Glossary

2-Abz - 2-Aminobenzoyl, usually combines with 2,4-dinitrophenyl (Dnp) or 3-nitro-tyrosine (NitroTyr) to form Fluorophore/Quencher pairs. excitation at 320 nm, emission at 420 nm.

3-Abz (m-aminobenzoic acid) can be seen as a γ-amino acid. When m-aminobenzoic acid is incorporated into peptide chains, it results in a rigid turn.

4-Abz (p-Aminobenzoic acid, PABA), being a naturally occurring benzoic acid derivative, can also be utilized as a rigid linear spacer.

Abu, L-α-Aminobutyryl ((S)-2-Amino-butanoyl),α-aminobutyric acid, is an amino acid derivative. Due to its structural similarity to natural amino acids, it is often used in the design and synthesis of peptides and peptide mimetics.

Ac represents acetyl. N-terminal acetylation is a common stabilizing modification for peptides in nature.

Acm, Acetamidomethyl, can be removed using Hg(II) or Ag(I). It is one of the commonly used thiol protecting groups for cysteine when synthesizing peptides with multiple disulfide bonds.

ACTH (adrenocorticotropic hormone) is a hormone secreted by the anterior pituitary that stimulates the adrenal cortex to produce corticosteroids.

Aad (L-α-aminoadipic acid) is a non-proteinogenic amino acid. Its structure is similar to glutamic acid (Glu), with an additional methylene group in its side chain.

(2-Aminoethoxy)acetic acid, also know as glycine ethyl ester or glycine ethylamide, can be used as a spacer or linker in peptide modification synthesis.

1-(1'-adamantyl)-1-methyl-ethoxycarbonyl, a very acid-labile amino protecting group in peptide synthesis, can be deprotected by 3% TFA/CH2Cl2

AFC (7-Amino-4-trifluoromethylcoumarin) is a fluorescent compound with an excitation of the released coumarin at 395-400 nm, emission at 495-505 nm.

Higher molecular weight species are formed due to the non-covalent adhesion of smaller species. In proteins in particular, aggregation is a form of denaturation that can occur on nonpolar surfaces with secondary structures, such as those that typically form intramolecular interactions and are buried in the α-helices and β-sheets of the protein. Molecules interact with each other, sometimes forming insoluble polymolecular forms. Aggregation contrasts with oligomerization, the normal interaction of correctly folded native proteins to form higher-order polymers..

AHX, Aminohexanoyl,6-amino hexanoic acid, also abbreviated Aca or LC, Typically introduced as a short non-polar spacer between biotin, fluorophores and peptide sequences.

2-Aminoisobutyric acid is a rare non-protein amino acid that is an end product of pyrimidine metabolism and is excreted in the urine and is present in some antibiotics of fungal origin. Also used to replace natural amino acids for peptide synthesis.

Alcohols are those organic compounds which are characterized by the presence of one, two or more hydroxyl groups (−OH) that are attached to the carbon atom in an alkyl group or hydrocarbon chain. Peptide alcohols are clinically crucial compounds that are insufficiently investigated in the structure-activity relationship (SAR) studies for drug discovery. For example, DAMGO is an opioid receptor agonist modified by alcohol at the C-terminal, with the sequence of Tyr-{d-Ala}-Gly-{Me-Phe}-Gly-ol. It has high selectivity and affinity for the μ-opioid receptor.

An aldehyde is an organic compound in which the carbonyl group is attached to a carbon atom at the end of a carbon chain. Peptide aldehydes are important tools in biochemistry and chemical biology for the inhibition and chemical disabling of proteases.

Aloc - Allyloxycarbonyl, amino protecting group (also abbreviated Alloc). Protection can be removed with Pd(PPh3)4.

Alzheimer's disease, marked by β-amyloid plaques and tau tangles, results from synaptic dysfunction and clearance pathway issues, causing cognitive impairment.

7-Amino-4-methylcoumarin (AMC) is a common fluorescent probe for peptide labeling in protease studies. Its conjugation to a peptide quenches the fluorescent signal, and the released AMC upon protease cleavage can quantify enzyme activity, with excitation/emission maxima of 345/445 nm. For instance, the preferred substrate fluorescent peptide for determining the trypsin-like activity of purified proteasome, with the sequence: Ac-Arg-Leu-Arg-AMC.

Atrial natriuretic peptide (ANP), a hormone produced and released by the atria of the heart in response to increased blood volume and pressure. It functions to regulate fluid balance and blood pressure by promoting vasodilation, increasing urine production (diuresis), and reducing sodium reabsorption in the kidneys. These actions help counteract the effects of high blood pressure and fluid overload in the body.

Antigenic peptides are short amino acid sequences derived from proteins or other biomolecules that trigger an organism's immune response. These peptides are recognized by the immune system as foreign or foreign to the body, leading to the activation of immune cells such as T cells and B cells. Antigenic peptides play a crucial role in immune responses, including adaptive antibody production and the development of immune memory. They are widely studied in immunology and vaccine development because of their potential to trigger specific immune responses against pathogens or abnormal cells.

The synthesis of asymmetric peptides with 2, 4, and 8 branches can be achieved by strategically inserting lysine, arginine, or glutamic acid into the peptide sequence.

Asymmetric dimethylarginine (ADMA, Arg(Me)2) is a naturally occurring chemical compound and an endogenous inhibitor of nitric oxide synthase (NOS). Fmoc-Arg(Me)2-OH (asymmetrical) can be directly used for the synthesis of peptides containing asymmetric dimethylarginine.

5-Aminovaleric acid,can be used as a spacer or linker in peptide modification synthesis.

Benzyloxymethyl (Bom) is an acid-labile imidazole protecting group used in the Boc-SPPS process for histidine-containing peptides. Benzyloxymethyl produces highly reactive formaldehyde after treatment with acid. Therefore, Bom is the best cleavaged in the presence of Cys, methoxyamine or other compounds that react with aldehydes.

β-amino acids have their amino group attached to the β-carbon, which is the second carbon atom away from the carboxyl group. The general structural formula for a β-amino acid can be represented as: R−CH(NH2)−COOH

B-type natriuretic peptide(BNP), a hormone produced mainly by the heart's ventricles in response to excessive stretching of heart muscle cells. It plays a crucial role in regulating blood pressure and fluid balance, primarily by promoting vasodilation and increasing sodium excretion through the kidneys.

t-Butyloxycarbonyl (Boc) is a very acid-labilea α-amino protecting group in peptide synthesis, can be cleavaged by TFA/methylene chloride (1:1), HCl in ethyl acetate or dioxane, 98% formic acid.

2-(4-Biphenylyl)isopropyloxycarbonyl (Bpoc) is a very acid-labilea α-amino protecting group in peptide synthesis, can be cleavaged by with 1% TFA/methylene chloride.

Peptides with 2, 4, and 8 branches can be achieved by strategically inserting lysine, arginine, or glutamic acid into the peptide sequence.

t-Butyldimethylsilyl (TBS or TBDMS) is a hydroxyl protecting group compatible with Fmoc-SPPS. It is acid-labile and can be selectively cleaved by fluoride ions.

Benzoyl is an acyl group often introduced at the N-terminus of peptides. It is less polar than acetyl (Ac) and can be as a permanent modification.

Benzyl (Bzl) an alkyl residue and a side-chain protecting group used for blocking alcohols (Ser, Thr, Hyp) in peptide synthesis. it is can be cleaved by strong acids or catalytic hydrogenolysis (e.g. hydrogen/Pd).

Cholecystokinin (CCK) is a peptide hormone produced by the mucosa of the upper intestine and found in the central nervous system. It stimulates gallbladder contraction, pancreatic enzyme release, and influences various gastrointestinal processes.

Calcitonin gene-related peptide (CGRP) is a 37-amino acid peptide related to calcitonin, amylin, and adrenomedullin. It exists in two forms, α-CGRP (CGRP I) and β-CGRP (CGRP II), with similar biological activities. CGRP is primarily found in sensory and central neurons, influencing cardiovascular function, calcium metabolism, and fetoplacental vascular tone. Its receptors are G-protein-coupled and activate adenylate cyclase, interacting with receptor activity modifying proteins (RAMPs) for ligand specificity and cellular trafficking.

L-Cyclohexylalanine (Cha) is a non-polar amino acid analog of phenylalanine, where the aromatic ring is replaced by a cyclohexane ring. This substitution allows studying the role of aromatic amino acids in interactions such as π-π interactions by replacing phenylalanine residues with Cha in experiments.

L-α-Cyclohexylglycine (Chg) is a non-polar amino acid that is sterically hindered. It serves as a significant pharmaceutical intermediate and is also found in natural products.

Cholesterol is produced naturally by the liver and other cells in the body, but it can also come from the food we eat, especially from animal products such as meat, poultry, and full-fat dairy products. Cholesterol can be linked to peptides to improve the pharmacokinetics.

cis-Hydroxyproline, the stereoisomer of natural trans-hydroxyproline.

Citrulline is present in proteins as a result of a post-translational enzymatic modification of arginine residues.

CMK is an RSK2 kinase inhibitor with similar potency but less chemical stability than FMK.

C-type natriuretic peptide (CNP) is a peptide by vascular endothelial cells, known for its vasodilatory effects. It exhibits structural and physiological similarities to atrial and brain natriuretic peptides (ANP and BNP).

L-α-Cyclopentylglycyl (Cpg), is a non-polar amino acid that is sterically hindered.

In peptide sequence, that unique residue which is connected to the linear sequence by its amino group, leaving it with a free carboxy group.This residue's carboxyl group can undergo modifications such as amidation or, in cases like pyroglutamate, internal lactamization.

Cyanine 3 is a red-fluorescent cyanine dye commonly excited by a light source around 558 nm and emitting light at approximately 572 nm.

Cyanine 5 is a cyanine dye fluorophore that emits near-infrared fluorescence commonly excited by a light source around 646 nm and emitting light at approximately 664 nm.

L-α,γ-Diaminobutyric acid is an α,ω-diamino acid, a shorter analogue of ornithine (Orn) and lysine (Lys). With appropriate protection, α,ω-diamino acids can be selectively modified at their Nω position or incorporated to create branched peptides or dendrimers.

3-(Dimethylaminoazo)benzene-4-carboxylic acid, is a chromophore linked to amino groups used in biochemistry and molecular biology applications as a quencher in fluorescence resonance energy transfer (FRET), e.g. with EDANS. Excitation of DABCYL at 454 nm.

Dabsyl ,4-dimethylaminobenzenesulfonyl chloride, A chromophore linked to amino groups used as a quencher in combination, e.g. with EDANS. Excitation of Dabsyl at 436 nm.

4-Dimethylamino-1-naphthalene-sulfonyl, a fluorophor linked to amino groups, excitation at 342 nm, emission at 562 nm.

L-α,β-Diaminopropionic acid (Dap or Dpr) is an α,ω-diamino acid, which is a shorter analogue of diaminobutyric acid (Dab), ornithine (Orn), and lysine (Lys). Modified derivatives of α,ω-diamino acids can be selectively altered at their Nω position or incorporated to create branched peptides or dendrimers.

1-(4,4-Dimethyl-2,6-dioxocyclohex-1-ylidene)ethyl (Dde) is an amino-protecting group used in peptide synthesis. It can be cleaved selectively using 2% hydrazine hydrate in dimethylformamide (DMF). Nω-Dde allows for the specific removal of Dde from amino acids such as Dap, Dab, Orn, or Lys after Fmoc solid-phase peptide synthesis (SPPS), facilitating on-resin modification of the Nω-amino group.

Disulfide bonds are covalent bonds formed between two sulfhydryl (-SH) groups of cysteine residues in proteins.

2,4-dimethoxybenzyl is an acid-labile formamide protecting group used for reversible backbone modification in peptide synthesis. They are incorporated during solid-phase peptide synthesis (SPPS) as the amino acid or dipeptide Fmoc-Dmb (Fmoc-Xaa-DmbYaa-OH), where Fmoc prevents peptide aggregation and thus promotes efficient elongation. Dmb also promotes cyclization reactions and prevents asparagimide formation. Unlike Hmb derivatives, Dmb does not form benzoxazepines during activation.

2,4-Dinitrophenyl is a chromophore that is conjugated to amino groups, commonly used as a quencher in fluorescence resonance energy transfer (FRET) substrates.

4,4′-Dimethoxydityl, also known as bis-(4-methoxyphenyl)methyl, is an acid-labile carboxamide protecting group that is compatible with Fmoc solid-phase peptide synthesis (SPPS).

DOPA, 3,4-dihydroxyphenylalanine, is a precursor to several crucial neurotransmitters, including dopamine, norepinephrine, and epinephrine.

(4,7,10-Tricarboxymethyl-1,4,7,10-tetraazacyclododecyl)-acetic acid, abbreviated as DOTA, is a cyclic chelator typically attached to the N-terminus of peptides. DOTA facilitates the labeling of peptides with radionuclides such as 68Ga or 90Y for various biomedical applications, including imaging and targeted therapy.

Diphenylmethyl (dityl), an acid-labile N-, O-, and S-protecting group.

Diethylenetriaminepentaacetic acid (DTPA) is a useful chelating agent for radionuclides such as (68)Ga, (99m)Tc and (111)In, which are applicable to nuclear medicine imaging.

5-[(2-Aminoethyl)amino]naphthalene-1-sulfonic acid (EDANS) is a fluorophore commonly linked to the Nω of diamino acids like lysine. It is frequently used in FRET substrates, typically paired with quenchers like DABCYL. EDANS has an excitation wavelength of 340 nm and emits at 490 nm.

Endothelial monocyte-activating polypeptide.

Ethyl, an alkyl group and homolog of methyl (Me), is used for permanent N- and S-ethylation modifications in peptides.

Epitope mapping (antigen epitope mapping) is a technique used to determine the specific areas (that is, antigen epitopes) on an antigen that can be recognized by antibodies or the immune system. Antigen epitopes can be divided into linear epitopes and conformational epitopes. Through antigen epitope mapping, we can deeply understand the relationship between the structure and function of the antigen, which is of great significance in vaccine development, disease diagnosis, immunotherapy and other aspects.
Some commonly used antigen epitope mapping methods include:
X-ray crystallography: It can directly analyze the three-dimensional structure of the antigen, thereby determining the position of the epitope.
Nuclear magnetic resonance: It can also be used to analyze the structure of the antigen to determine the epitope.
Peptide scanning technique: Using a series of overlapping synthetic peptide segments to identify the epitope that binds to the antibody.
For example, in vaccine research and development, clarifying the key epitopes on the antigen helps to design more effective vaccines and induce a more targeted immune response; in disease diagnosis, determining the antigen epitopes related to specific diseases can develop more accurate diagnostic reagents.

5-FAM (5-Carboxyfluorescein) is a fluorophore commonly used for labeling biomolecules, with an excitation wavelength of 490 nm and emission at 520 nm.

Fluorescein-6-carbonyl is a fluorophore attached to amino groups, with an excitation wavelength of 490 nm and emission at 520 nm.

Fluorescein isothiocyanate (FITC) is a fluorophore that reacts with amino groups. When tagging a peptide at its N-terminus with FITC, a spacer like β-alanine or Ahx commonly be inserted. FITC has an excitation wavelength of 490 nm and emission at 520 nm.

9-Fluorenylmethyl is a base-labile protecting group used for O- and S-protection.

FMK, fluoromethyl ketone, is an irreversible inhibitor of RSK2 kinase.

9-Fluorenylmethoxycarbonyl (Fmoc), the α amino protecting group in FMOC solid-phase synthesis, can be removed with 20% piperidine/DMF.

Formyl is an indole protecting group used in Boc-SPPS. Trp(For) is cleaved by HF in the presence of a mercaptan or by bases such as piperidine.

Fluorescence resonance energy transfer (FRET) is the transfer of nonradiative energy from an excited fluorophore (donor) to a suitable acceptor (quencher). The transfer depends on distance, dipole orientation, and spectral overlap of the donor and acceptor. In FRET substrates, the fluorophore and quencher are linked via a peptide chain. Enzymatic cleavage increases fluorescence by separating donor and acceptor.

Fluorescence is the light emitted by a substance that absorbs light or other electromagnetic radiation. This occurs when molecules called fluorophores absorb photons of a specific wavelength, become excited, and then emit photons and return to their ground state. The emitted light typically has a longer wavelength and lower energy than the absorbed light, resulting in a characteristic fluorescence spectrum. This phenomenon is widely used for a variety of scientific and medical purposes, including microscopy, flow cytometry, and fluorescence spectroscopy.

Gastric inhibitory polypeptide (GIP), also known as glucose-dependent insulinotropic peptide, belongs to the secretin family of hormones. It stimulates insulin secretion, inhibits gastric acid secretion, and plays a crucial role in regulating insulin secretion and glucose homeostasis.

L-γ-Carboxyglutamic acid (Gla) is formed through the post-translational carboxylation of glutamic acid, resulting in proteins capable of binding calcium ions, such as osteocalcin. Gla-containing peptides are ideally synthesized using Fmoc solid-phase peptide synthesis (SPPS), as Gla can undergo decarboxylation to yield glutamic acid in the presence of strong acids.

Glucagon-like peptides are members of the glucagon superfamily of peptide hormones derived from the C-terminal region of proglucagon. They are primarily synthesized by intestinal L cells.

Gonadotropin-releasing hormone (LHRH) is a decapeptide hormone produced in hypothalamic neurosecretory cells and released in pulsatile bursts into the pituitary portal circulation. Pulsatile secretion is critical for reproductive functions, sexual development, and differentiation.

Growth hormone-releasing hormone (GHRH), also known as somatorelin, is a hypothalamic peptide hormone that stimulates the pituitary gland to release and synthesize growth hormone.

Growth hormone-releasing hormone (GHRH), also known as somatorelin, is a hypothalamic peptide hormone that stimulates the pituitary gland to release and synthesize growth hormone.

Human leukocyte antigen (HLA) refers to a group of proteins found on the surface of cells that play a crucial role in the immune system's recognition of foreign substances. They are encoded by the major histocompatibility complex (MHC) genes in humans and are essential for the presentation of antigens to T cells, enabling the immune system to distinguish between self and non-self cells. HLA molecules are highly diverse and polymorphic, contributing significantly to individual immune responses and susceptibility to autoimmune diseases and transplant rejection.

2-hydroxy-4-methoxybenzyl is an acid-labile formamide protecting group used for reversible backbone modification in peptide synthesis. It is incorporated as an amino acid or Fmoc-Hmb dipeptide (Fmoc-Xaa-HmbYaa-OH) during solid-phase Fmoc peptide synthesis (SPPS), preventing aggregation and enabling efficient peptide extension. Hmb also aids in cyclization reactions and prevents asparagine formation.

L-Homoarginine is a homologue of L-arginine, abbreviated as Har, and can be found in plasma and urine. Homoarginine is the result of guanidination of lysine, which can also be performed on peptides and proteins.

Homocitrulline is a homolog of L-citrulline, abbreviated as Hci, and can be detected in human urine.

L-homocysteine is a homologue of cysteine, abbreviated as Hcy, and is produced by the demethylation of methionine. Elevated blood Hcy levels are a risk factor for cardiovascular and neurodegenerative diseases. In contrast to Cys derivatives, Hcy derivatives do not racemize during coupling, nor does β-elimin.

Homologues of L-leucine, abbreviated as Hle.

Homophenylalanine, a homologue of phenylalanine, abbreviated as Hph, is a component of ACE and renin inhibitors. Fmoc-Homophe-OH is a potential anti-inflammatory drug.

L-homoproline or L-picolic acid, abbreviated as Pip or Hpr. The proline homologue Hpr is a degradation product of L-lysine. Both enantiomers can be detected in human plasma. Since proline residues strongly influence the conformation of the peptide, replacing Pro with Hpr (or azetidine-2-carboxylic acid (Aze)) can modulate its secondary structure.

L-transhydroxyproline is produced post-translationally by the oxidation of proline. Hyp is a major component of collagen and mussel protein.

Isoserine, an isomer of L-serine, is a β-amino acid.

ivDde, an amino protecting group, can be deprotected and cleaved by 2% hydrazine hydrate in DMF. ivDde is more stable than Dde to frequent multiple piperidine treatments during Fmoc-SPPS. Nω-ivDde can be selectively removed from Dap, Dab Orn, or Lys, allowing post-synthetic on-resin modification of the Nω-amino group.

Keyhole limpet hemocyanin (KLH) is a large oxygen-carrying multisubunit metalloprotein found in the hemolymph of giant keyhole limpet hemocyanin. As an antigen carrier, KLH usually enhances immunogenicity and antigen-fixing capabilities by coupling target polypeptide sequences, significantly promoting the generation of efficient, specific and functional antibodies.

Luteinizing hormone-releasing hormone (LHRH or GnRH) is a decapeptide hormone synthesized by neurosecretory cells within the hypothalamus and released pulsatilely into the pituitary portal circulation. Pulsatile secretion is critical for reproductive function, sexual development, and differentiation.

In peptide design and synthesis, reserachers can insert a linker between the biotin or fluorescent and the peptides. A common hydrophobic spacer is aminohexanoic acid (Ahx), and a common hydrophilic spacer is poly(ethylene) glycol (PEG).

Freeze-drying process, which removes liquid from heat-sensitive materials. The material is frozen, placed under high vacuum, and kept at low temperatures. The pressure created by the vacuum causes the ice to change from solid to gaseous state without passing through the liquid state. Peptides are usually delivered as lyophilized powder.

Liquid Chromatography-Mass Spectrometry is a versatile analytical technique that integrates liquid chromatography with mass spectrometry to provide detailed information about the composition and structure of molecules within complex samples.

Multiple Antigenic Peptides. Multiple Antigenic Peptide is a one potent way to produce high-titer anti-peptide antibodies and synthetic peptide vaccines.

Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry (MALDI-MS) is an analytical technique used to measure the mass-to-charge ratio of ions. It's particularly useful for the analysis of biomolecules like peptides, proteins, and polymers.

Mass spectrometry (MS) is a powerful analytical technique used to measure the mass-to-charge ratio (m/z) of ions.

4-Methoxy-β-naphthylamide, abbreviated as MNA, is a fluorophore that is usually attached to a carboxypeptidase substrate at the C terminus. Cleaved 4MβNA excites at 335-350 nm and emits at 410-440 nm

Methoxybenzenesulfonyl (Mbs) is a guanidyl protecting group used in Boc-based solid-phase peptide synthesis (Boc-SPPS). This protecting group can be deprotected by cleavage with hydrogen fluoride (HF).

4-Methylbenzyl (Mbzl) is a sulfhydryl protecting group used in Boc-based solid-phase peptide synthesis (Boc-SPPS). Mbzl is more stable than methoxybenzyl (Mob) under frequent trifluoroacetic acid (TFA) treatments and can be removed by hydrogen fluoride (HF) cleavage.

(7-Methoxycoumarin-4-yl)acetic acid (Mca) is a fluorophore that can be linked to an amino group.
Mca binds to dinitrophenyl (Dnp) for fluorescence resonance energy transfer (FRET) substrates. The excitation wavelength is 325 nm, and the emission wavelength is 392 nm.

Melanin-concentrating hormone (MCH) is a cyclic neuropeptide first isolated from fish and rats. MCH is primarily involved in regulating skin pigmentation in teleost fish and feeding behavior in mammals.

Methyl, the simplest alkyl substituent, is involved in N-, O-, and S-methylation, which constitute permanent modifications of the peptide.

3-Methoxysuccinyl, corresponding to deaminated Asp(OMe), is a polar N-terminal blocking group commonly incorporated into carboxypeptidase substrates.

Methylation is a post-translational modification (PTM) of peptides and proteins where a methyl group (-CH3) is enzymatically added to specific amino acid residues, commonly lysine (Lys), arginine (Arg), histidine (His), or glutamate (Glu). This modification can significantly influence protein function, stability, and interactions with other molecules, thereby playing pivotal roles in regulating diverse cellular processes including gene expression, signal transduction, and protein-protein interactions.

The major histocompatibility complex (MHC) is a genetic region containing genes that encode MHC molecules. These molecules play a crucial role in the immune system and in autoimmunity. In humans, this complex is also known as the human leukocyte antigen (HLA) system.

MHC class I (MHC I) molecules are proteins on cell surfaces that present peptides from inside the cell to cytotoxic T cells. This helps immune cells recognize and destroy infected or abnormal cells, crucial for immune defense against pathogens and cancer.

MHC class II (MHC II) molecules are cell surface proteins that present peptides derived from foreign substances to helper T cells. This interaction is essential for coordinating immune responses and activating other immune cells against pathogens.

Monomethylated arginine (MMA) is a post-translational modification where a single methyl group (-CH3) is enzymatically added to the guanidino nitrogen of an arginine residue within a peptide or protein

3-mercaptopropylamine,can be used as a peptide ligand or modifier in various biochemical and biomedical applications.

Myristoylation is a lipid modification process wherein a myristoyl group, consisting of a 14-carbon saturated fatty acid, is covalently linked to the N-terminus of peptide. This modification serves to anchor the protein to the cell membrane, facilitating its localization and participation in diverse cellular processes.

β-(1-naphthyl)-L-alanine is a nonpolar amino acid derivative similar to phenylalanine, but with a naphthyl group instead of a phenyl group.

β-(2-Naphthyl)alanine is a nonpolar amino acid derivative similar to phenylalanine, but with a naphthyl group instead of a phenyl group.

3-nitrobenz-2-oxa-1, 3-diazole (NBD) is usually introduced by conjugating the reagent NBD-Cl to the peptide. NBD-labeled peptides are widely chosen for their utility in studies focusing on membranes and cell biology.

N-Ethylamide can be considered as a decarboxylated form of C-terminal alanine. In the LHRH agonist buserelin, NHEt serves as an analog of C-terminal glycinamide. Peptide N-ethylamide is resistant to degradation by carboxypeptidases.

L-norleucine (Nle) is a stable isostere of L-methionine. When the biological activity of a peptide is compromised due to sulfoxide formation, Nle can be substituted for Met without typically altering its functional behavior.

NOTA, 1,4,7-triazacyclononane-1,4,7-triacetic acid, is a bifunctional chelator that serves as a framework for constructing PET imaging tools. It is also utilized in probe design and signal amplification through multivalent effects and holds potential applications as a diagnostic gallium radiopharmaceutical.

N-Me usually refers to N-methylation, a chemical modification in which a methyl group (-CH 3 ) is attached to a nitrogen atom in the molecule, such as N-Me-Gly, N-Me-Ser, N -Me-Tyr, N-Me-Thr, N-Me-Asp, N-Me-Glu, N-Me-Ala, N-Me-Phe, N-Me-Leu, N-Me-Ile, N-Me -Val, N-Me-Met, N-Me-Nle, N-Me-Nva, etc.

NODAGA,1,4,7-triazacyclononane,1-glutaric acid-4,7-diacetic acid, is an outstanding bifunctional chelator for the design and development of organometallic radiopharmaceuticals, offering significant potential for applications in diagnostic imaging and targeted radiotherapy.

2-Nitrophenylthio (Nps) is an S-protecting group used in Boc-based solid-phase peptide synthesis (Boc-SPPS). It can be cleaved by thiols, specifically through the free sulfhydryl group of cysteine (Cys), leading to the simultaneous formation of a disulfide bond.

Neuropeptide Y (NPY) is a prominent neuropeptide in the brain and part of the neuropeptide Y family, which includes pancreatic polypeptide (PP) and peptide YY (PYY).

2-Nitro-2-pyridylsulfenyl (Npys) is an S-protecting group that is compatible with Boc-based solid-phase peptide synthesis (Boc-SPPS). Npys can be cleaved by thiols, specifically through the free sulfhydryl group of cysteine (Cys), resulting in the simultaneous formation of a disulfide bond.

Norvaline is a nonpolar aliphatic amino acid and a homolog of α-aminobutyric acid (Abu).

α-Naphthylamide is a fluorophore commonly used in carboxypeptidase substrates, typically linked at the C-terminus of peptides. Cleaved αNA excites at 330 nm and emits at 370 nm.

α-Naphthylamide is a fluorophore commonly used in carboxypeptidase substrates, typically linked at the C-terminus of peptides. Cleaved βNA at 320-340 nm, emission at 410-420 nm.

Allyl ester is a carboxyl protecting group that is compatible with both Fmoc- and Boc-based solid-phase peptide synthesis (SPPS). Similar to Aloc, allyl esters can be selectively removed by treatment with Pd(PPh3)4. In Fmoc-SPPS, Asp(OAll) is susceptible to base-catalyzed formation of aspartimide.

Benzyl ester, a carboxyl protecting group, can be removed by catalytic hydrogenation (e.g. H2/Pd) or strong acids.

OcHex is the standard carboxyl protecting group used in Boc-based solid-phase peptide synthesis (Boc-SPPS).

4-(N-[1(4,4-Dimethyl-2,6-dioxocyclohexylidene)-3-ethylbutyl]amino)benzyl ester (ODmab) is a carboxyl protecting group used in Fmoc-based solid-phase peptide synthesis (Fmoc-SPPS). It can be cleaved and deprotected using 2% hydrazine hydrate in DMF.

2,4-Dimethoxybenzyl ester is a highly acid-labile carboxyl protecting group that can be removed using 1% TFA in dichloromethane.

Ethyl ester, Due to the stringent conditions required for the removal of ethyl esters, modifying peptides with ethyl esters can enhance their lipophilicity and stability.

9-Fluorenylmethyl ester is a base-labile carboxyl protecting group that can be removed using piperidine in DMF.

Hexyl esters, Due to the stringent conditions required for the removal of ethyl esters, modifying peptides with ethyl esters can enhance their lipophilicity and stability.

L-Otahydroindole-2-carboxylic acid (Oic) is a nonpolar hindered amino acid. The insertion of this proline-related amino acid into the polypeptide sequence strongly affects the conformation of the peptide.

Methyl esters are semi-permanent C-terminal protecting groups in liquid-phase synthesis, and they can be converted into peptide hydrazides, precursors of reactive peptide azides. Azide coupling remains the most popular fragment coupling method in liquid-phase peptide synthesis.

3-Methylpent-3-yl ester (OMpe) is an acid-labile carboxyl protecting group frequently employed to protect the carboxyl group of aspartic acid (Asp) in Fmoc-based solid-phase peptide synthesis (Fmoc-SPPS).This more sterically demanding tert-butyl ester analogue was developed specifically to reduce base-catalyzed asparagimide formation.

Ortho-nitrophenyl esters of Boc- or Z-amino acids are preactivated derivatives used in peptide solution synthesis.

Ornithine (Orn) is produced from arginine during the urea cycle and can also be observed in peptides as an arginine degradation product. Orn formation via acylation of the guanidine moiety of arginine is a common side reaction in peptide synthesis.

Hydroxysuccinimide ester (OSu, abbreviated as NHS) is a preactivated amino acid derivative that is commonly used in peptide synthesis, especially peptide modification. OSu esters are safe, non-steric, compatible with aqueous systems and easy to handle.

Tert-butyl ester, an acid-labile carboxyl protecting group for amino acids in peptide synthesis.

4-aminobenzoic acid (para-aminobenzoic acid), Can be used to for the synthesis of antibody-drug conjugate linkers. For example, Mal-PEG2-Val-Cit-PABA is a cleavable antibody drug conjugate (ADC) linker.

PABC (para-aminobenzyl carbamate) is a chemical compound used in the synthesis of antibody-drug conjugates (ADCs) as a linker. It facilitates the attachment of drugs to antibodies in a controlled manner, enabling targeted drug delivery in cancer therapies and other biomedical applications. For example, Mc-Val-Cit-PABC-PNP is a cathepsin-cleavable linker utilized in antibody-drug conjugates (ADCs).

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a highly conserved neuropeptide prominently expressed throughout the mammalian brain. It exerts its biological effects by enhancing intracellular cyclic AMP levels through receptor interaction.

Palmitoyl, a nonpolar acyl group introduced at the N-terminus or side. Palmitoylation has also been observed as a post-translational modification of proteins.

Phenylacetamide methyl resin is a resin designed specifically for Boc-based solid-phase peptide synthesis (Boc-SPPS). Peptides synthesized on this resin can be released using HF cleavage.

In Antibody-Drug Conjugates (ADCs), the linker connects the antibody to the cytotoxic payload. The choice of payload is critical as it determines the effectiveness and specificity of ADCs in delivering therapy to target tissues through specific release mechanisms.

2,2,4,6,7-Pentamethyldihydrobenzofuran-5-sulfonyl (Pbf) is the preferred guanidino protecting group used in Fmoc-based solid-phase peptide synthesis (Fmoc-SPPS). It exhibits slightly higher acid-lability compared to Pmc.

Penicillamine is an analog of L-cysteine characterized by the substitution of a methyl group (-CH3) with a carboxylic acid (-COOH).

Peptide self-assembly is when peptides naturally arrange themselves into ordered structures without external intervention. this process is driven by non-covalent interactions such as hydrogen bonding, hydrophobic interactions, electrostatic forces, and π-π stacking. Peptide self-assembly can lead to the formation of various nanostructures including fibers, spheres, sheets, and gels, which have applications in materials science, biotechnology, and medicine.

Phenylacetyl (Phenylac or Phac) is an acyl group typically linked at the N-terminus of peptides, characterized by lower polarity compared to acetyl (Ac). It constitutes a permanent modification of peptides.

phenylglycine (Phg) is an amino acid derivative where a phenyl group substitutes for the hydrogen atom in the glycine molecule

Peptide Histidine Isoleucine (PHI), a porcine peptide related to VIP and secretin.

Peptide histidine methionine (PHM), a human peptide related to VIP.

The isoelectric point (pI) is defined as the level of pH at which the protein/peptide has a net charge of zero (Smoluch et al., 2016).

2,2,5,7,8-Pentamethylchroman-6-sulfonyl (Pmc) is a guanidinyl protecting group commonly used in Fmoc-based solid-phase peptide synthesis (Fmoc-SPPS). It is noted for being slightly less acid-labile compared to Pbf.

p-Nitroaniline, a chromophore, is typically conjugated to the C-terminus of carboxypeptidase substrates. The absorption of the liberated p-nitroaniline is commonly measured at wavelengths around 405 or 410 nm.

L-Propargylglycine (Pra) is produced by microorganisms. This amino acid, characterized by its triple-bond structure, is highly regarded as a foundational unit for synthesizing peptides capable of engaging in "click chemistry" reactions, garnering significant attention in the field.

Parathyroid hormone (PTH) is a peptide hormone released by the parathyroid glands, crucial for maintaining calcium and phosphorus homeostasis in the extracellular fluid.

Post-translational modifications (PTMs) of proteins add functional groups or proteins, cut regulatory subunits, or break down entire proteins. These changes, like phosphorylation, glycosylation, methylation, acetylation, lipidation, ubiquitination, nitrosylation, and proteolysis, affect how cells work normally and during disease. Understanding PTMs is crucial for basic research and finding new treatments.

pyroglutamic acid, also known by abbreviations such as Pgl, Glp, pGlu, or

phenylazobenzylmethoxycarbonyl is a chromophoric N-protecting group used in peptide synthesis, cleavable by catalytic hydrogenation or strong acid. It exhibits maximum absorption wavelengths at 229 nm, 320 nm, and 441 nm.

A quencher pair consists of a fluorescent molecule (fluorophore) and a quencher molecule used in fluorescence-based research and assays. The quencher absorbs the light emitted by the fluorophore, reducing its fluorescence. When the fluorophore and quencher are separated, such as through a biochemical reaction, the fluorescence signal increases. This allows researchers to measure real-time changes and interactions. This technique is commonly used in applications like real-time PCR, molecular probes, and FRET (Förster Resonance Energy Transfer) assays.

Fluorine-18 is a radioligand commonly used in PET imaging to assess glucose metabolism in tissues and is commonly used in cancer diagnosis and brain imaging.

A random peptide library is a collection of many short peptide sequences generated randomly. Each peptide in the library has a specific number of amino acids with randomly determined sequences, creating a diverse range of peptide molecules. Researchers use these libraries to screen for peptides with specific properties, biological activities, or interactions with target molecules. They are especially useful in drug discovery, immunology, and studies of protein-protein interactions, helping to identify new therapeutics and understand complex biological processes.

A residue is an individual amino acid within a peptide or protein. As amino acids join together through peptide bonds to form these chains, each amino acid unit is termed a residue. This term is used because during the formation of the peptide bond, each amino acid loses a water molecule (H2O), leaving behind what is referred to as a residue.

Resin is an insoluble polymer used in solid-phase peptide synthesis (SPPS) as a solid support for the continuous addition of amino acids. Resin beads provide a stable and inert surface to which the initial amino acids are covalently attached, allowing the peptide chain to be built residue-by-residue.

Rhodamine B is a bright pink to red dye with an excitation wavelength usually around 540-570 nm and an emitted light range of 560-580 nm. It is usually conjugated to the peptide sequence via the N-terminal amino group of the peptide

Reversed-phase high-performance liquid chromatograph.

Structure-Activity Relationship (SAR) drugs are developed by studying the relationship between a drug's chemical structure and its biological activity.

Sarcosine, the simplest N-alkylated amino acid.

Symmetrical dimethylarginine(SDMA, Arg(Me)2), Fmoc-Arg(Me)2-OH (symmetrical) can be directly used for the synthesis of peptides containing symmetric dimethylarginine.

Solid-phase peptide synthesis (SPPS) is a method for the chemical synthesis of peptides, where peptides are assembled stepwise on a solid support or resin by sequentially adding protected amino acids. SPPS encompasses two strategies: Fmoc-SPPS and Boc-SPPS, which differ in the choice of Nα-amino group protecting groups (Fmoc or Boc) and side chain protecting groups. The type of Nα-amino protecting group selected dictates the side chain protection strategy and the conditions for the final cleavage of the peptide from the resin.

Statine, abbreviated as Sta, is a non-protein amino acid that is often used in the design of peptide mimetics, especially in the synthesis of protease inhibitors.

Tert-Butylthio (StBu) is an S-protecting group that is cleaved by phosphine reduction and is compatible with Boc-SPPS.

Succinyl is a polar N-terminal modification that corresponds to deaminated aspartate and is typically incorporated into carboxypeptidase substrates.

TAMRA, also abbreviated as TMR, is a fluorophore that can be attached to an amino group. It is often used in combination with FAM for FRET substrates. TAMRA has an excitation wavelength of 485 nm and an emission wavelength of 535 nm.

Tert-butyl is an acid-labile protecting group commonly used for alcohols and phenols, which can be cleaved using trifluoroacetic acid (TFA).

Triethylammonium phosphate is a buffer used in reversed-phase HPLC mobile phases.

Trifluoroacetic acid (TFA) was used for the peptide cleavage from resin in Fmoc-SPPS and for the removal of tBu-derived protecting groups.

Trifluoromethanesulfonic acid (TFMSA) is a stronger acid than TFA. TFMSA can be used as a safer alternative to highly toxic HF for the final cleavage step of the Boc-SPPS strategy.

L-tert-leucine (Tle) is a nonpolar amino acid with sterically demanding side chains that destabilizes α-helices.

2,4,6-Trimethoxybenzyl is an acid-labile Asn and Gln amide protecting group used in Fmoc-SPPS.

Tosyl is used as a protecting group for guanidine and imidazole in Boc-SPPS, and can be removed by Na/NH3

Trityl (Trt) is an acid-labile protecting group employed for Asn, Cys, Gln, and His residues in Fmoc-SPPS. It can be selectively removed using trifluoroacetic acid (TFA).

Pure peptides typically exist in a white powder state after freeze-drying.

Vasoactive intestinal peptide (VIP) is a 28-amino acid peptide belonging to the glucagon-ghrelin-secretin peptide superfamily.

9-Xanthydryl (Xan) is an acid-labile amide protecting group utilized for Asn and Gln residues in Boc-SPPS. Xan can be selectively removed using TFA.

When the peptide is labeled with FAM fluorescein, the lyophilized powder typically exhibits a yellow appearance.

Z-benzyloxycarbonyl, abbreviated as Z or Cbz, is used as an amino protecting group in peptide synthesis. It can be removed using hydrogenolysis or strong acids as neat HF or HBr/acetic acid.