Peptide Glossary

A post-translational modification where the C-terminal carboxyl group is converted to an amide (-CONH₂). Catalyzed by PAM (Peptidylglycine α-Amidating Monooxygenase). Essential for activity of ~50% of neuropeptides.

Host defense peptides that kill bacteria, fungi, or viruses. Often cationic and amphipathic, targeting microbial membranes. Examples include defensins, cathelicidins, and magainins.

An α-helix with segregated hydrophobic and hydrophilic faces. Key structural feature of antimicrobial peptides that enables membrane insertion and disruption.

Insoluble fibrillar protein aggregates with cross-β sheet structure. Associated with diseases (Alzheimer's Aβ, Parkinson's α-synuclein) but also have functional roles.

The ability of different ligands to selectively activate specific downstream pathways (e.g., G-protein vs. β-arrestin) through the same receptor. Therapeutic implications for reducing side effects.

The fraction of administered drug reaching systemic circulation. Oral peptides typically have <1% bioavailability due to GI degradation and poor permeability.

A family of antimicrobial peptides stored as inactive precursors and released by proteolytic cleavage. LL-37 is the only human cathelicidin, forming amphipathic helices in membranes.

Short peptides (typically <30 AA) capable of crossing cell membranes, often rich in arginine and lysine. Used to deliver cargo (proteins, nucleic acids, drugs) into cells.

Proteins that assist other proteins in achieving proper folding. Hsp70 'holdases' prevent aggregation; chaperonins (Hsp60) provide isolated folding chambers.

Venom peptides from cone snails, typically 10-30 AA with multiple disulfide bonds. Target ion channels with high specificity. Ziconotide (ω-conotoxin) is FDA-approved for pain.

Chemicals that activate carboxyl groups for amide bond formation in SPPS. Examples include HATU, HBTU, DIC, and EDC. Critical for efficient peptide synthesis.

Connecting ends of a peptide to form a ring, reducing conformational flexibility. Can be head-to-tail, disulfide, or lactam-bridged. Improves stability and often bioavailability.

Small (29-45 AA), cationic antimicrobial peptides with 3 conserved disulfide bonds. α-defensins are found in neutrophils; β-defensins in epithelial tissues. Part of innate immunity.

Covalent bond between cysteine sulfur atoms (-S-S-), stabilizing protein structure. Common in secreted proteins and peptides. Can be intra- or intermolecular.

A serine protease that cleaves dipeptides from the N-terminus of proteins with proline or alanine at position 2. Rapidly inactivates GLP-1 and GIP, limiting their half-life to ~2 minutes.

Environmental factor measuring kg waste per kg product. Traditional SPPS has E-factors of 3,000-50,000, indicating substantial environmental impact.

A receptor that recycles IgG and albumin by binding them at endosomal pH and releasing them at physiological pH. Exploited for half-life extension of peptide drugs.

The process of protein aggregation into amyloid-like fibrils. In insulin, exposure of the LVEALYL motif triggers cross-β sheet formation and therapeutic inactivation.

9-Fluorenylmethoxycarbonyl group, the most common N-terminal protecting group in modern SPPS. Removed by base (typically piperidine) to allow the next amino acid coupling.

A 30-amino acid incretin hormone released from intestinal L-cells. Stimulates insulin secretion, inhibits glucagon, slows gastric emptying, and promotes satiety. Target of blockbuster drugs (semaglutide).

Seven-transmembrane receptors that transduce signals via heterotrimeric G-proteins. ~80% of peptide hormones act through GPCRs, activating second messengers like cAMP, IP₃, and Ca²⁺.

A complex of six protein subunits. Insulin is stored as zinc-stabilized hexamers in β-cell granules and pharmaceutical formulations, providing stability.

The thermodynamic driving force for protein folding, where burial of nonpolar residues releases ordered water molecules, increasing entropy. Dominant force in tertiary structure formation.

Proteins or protein regions that lack stable tertiary structure under physiological conditions, existing as dynamic conformational ensembles. Important in signaling and phase separation.

Gut hormones (GLP-1, GIP) that stimulate insulin secretion after eating. Account for 50-70% of postprandial insulin response. Targets of diabetes therapeutics.

Protein segments that catalyze their own excision and join flanking sequences (exteins). Used to generate C-terminal thioesters for expressed protein ligation.

Covalent attachment of fatty acids to peptides. Enables albumin binding and FcRn-mediated recycling, dramatically extending half-life (e.g., semaglutide uses C18 diacid).

The process by which proteins (especially IDPs) demix from the bulk cytoplasm to form concentrated liquid droplets, creating membraneless organelles like stress granules, P-bodies, and nucleoli.

Analytical technique measuring mass-to-charge ratio of ions. Essential for peptidomics, enabling identification, sequencing, and quantification of peptides in complex samples.

Chemical synthesis using mechanical energy (ball milling) instead of solvents. Enables near-solvent-free peptide synthesis with dramatically reduced waste.

A chemoselective reaction joining a peptide C-terminal thioester with another peptide's N-terminal cysteine to form a native peptide bond. Enables chemical synthesis of full-length proteins.

Peptidylglycine α-Amidating Monooxygenase, the enzyme responsible for C-terminal amidation. Requires copper, ascorbate, and oxygen. Essential for neuropeptide maturation.

Targeted therapeutics combining a homing peptide, cleavable linker, and cytotoxic payload. Smaller than antibody-drug conjugates with better tumor penetration.

Attachment of polyethylene glycol (PEG) chains to peptides/proteins. Increases hydrodynamic radius, reduces renal clearance, extends half-life, and reduces immunogenicity.

Covalent cross-linking (typically with hydrocarbon chains) that locks peptides into α-helical conformations. Improves stability, protease resistance, and cell permeability.

The systematic study of all peptides in a biological sample, focusing on native endogenous peptides rather than tryptic digests. Uses mass spectrometry for analysis.

A molecule designed to mimic a peptide's structure and function while improving pharmacokinetic properties (stability, permeability, oral bioavailability).

Oligomers of N-substituted glycines where the side chain is on the nitrogen rather than the α-carbon. Completely resistant to proteases due to lack of backbone amides.

A left-handed, extended helix without internal hydrogen bonds. Major component of what's called 'random coil' in peptides. Important in proline-rich sequences.

Specialized serine proteases that cleave prohormones at specific sites (usually after basic residues like Lys-Arg or Arg-Arg) to release active peptide hormones. PC1/3 and PC2 are the major convertases in neuroendocrine tissues.

An inactive precursor form containing the mature peptide sequence plus additional pro-regions. Requires proteolytic processing for activation.

The cellular network maintaining protein homeostasis through synthesis, folding, and degradation pathways. Includes chaperones, ubiquitin-proteasome system, and autophagy.

Treatment using radiolabeled peptides that target overexpressed receptors on tumors. Lutathera (¹⁷⁷Lu-DOTATATE) targets somatostatin receptors in neuroendocrine tumors.

Membrane receptors with intrinsic kinase activity. Ligand binding induces dimerization and autophosphorylation. Used by larger peptides like insulin.

Small intracellular signaling molecules activated by receptors. Include cAMP (from Gαs), IP₃ and DAG (from Gαq), and Ca²⁺. Amplify and propagate signals.

An N-terminal sequence (15-30 AA) that directs nascent proteins to the secretory pathway. Cleaved by signal peptidase in the ER. Typically has hydrophobic core.

Sodium N-[8-(2-hydroxybenzoyl)amino] caprylate, a permeation enhancer enabling oral peptide absorption. Used in Rybelsus (oral semaglutide) to buffer pH and facilitate transcellular transport.

Chemical synthesis method where the growing peptide chain is attached to an insoluble resin. Amino acids are added sequentially from C to N terminus, with coupling and deprotection cycles.

A bacterial transpeptidase that recognizes LPXTG motifs and links them to oligoglycine nucleophiles. Used for site-specific protein labeling and chemo-enzymatic peptide synthesis.

A four-residue secondary structure motif that reverses chain direction. Common in cyclic peptides and at helix termini. Types I, II, and III are most prevalent.