Peptide Glossary

This glossary explains words you will meet in the Peptides & Modern Research library. It is for understanding only. It does not describe how any product is made, prepared, stored or used, and it gives no advice about starting, stopping or changing a medicine. Regulatory terms describe the United States unless another place is named; laws and agency practices change, and this is not legal advice. Entries link to the page that owns the topic.

Building blocks

• Amino acid. The basic building block of proteins; there are 20 different amino acids. [1]
• Peptide. A short chain of amino acids joined by chemical bonds. One genetics glossary gives "typically 2 to 50" amino acids, while a review of therapeutic peptides describes them as usually 500 to 5,000 daltons in weight. [2][3] Because sources measure differently, there is no single length cutoff; see peptides versus proteins.
• Peptide bond. The chemical link between neighboring amino acids in a chain. [2]
• Polypeptide. A longer chain of linked amino acids (51 or more in that glossary). Proteins are made of one or more polypeptides. [2][4]
• Protein. A large, complex molecule made of one or more long, folded polypeptide chains, needed for the structure, function and regulation of the body's tissues. [4]
• Sequence. The order of amino acids in a chain. For a protein it is determined by the DNA sequence of the gene that encodes it. [4] See peptide bonds and sequences.
• Cyclic peptide. A peptide whose chain forms a ring. Cyclic peptides can resist some digesting enzymes because the structure is less flexible than that of linear peptides. [5]
• Non-natural amino acid. An amino acid not found in the standard set, such as a D-amino acid. Researchers insert them into peptide sequences, especially at spots where enzymes cut, as a strategy to extend a peptide drug's half-life. [3]
• Chemical modification. Changes made to a peptide using medicinal chemistry to stabilize it or improve its activity, selectivity and solubility. [3]
• PEGylation. Attaching polyethylene glycol to a molecule. In proteins it can reduce kidney clearance and shield against digestion by enzymes. [3] See lipidation, PEGylation and cyclization.
• Analogue. A molecule modified from a natural one. Liraglutide, for example, is a GLP-1-derived drug changed at one position of the natural sequence, and degarelix was optimized from GnRH but acts as an antagonist. [3]
• Synthetic, recombinant and natural. Early peptide medicines came from natural sources. Synthetic oxytocin and vasopressin and recombinant human insulin were developed later. [3] "Synthetic" says how a molecule is made, not whether it is safe or effective. See natural, synthetic and modified peptides.

Signals, receptors and hormones

• Hormone. One of the body's chemical messengers, traveling in the bloodstream to tissues or organs. [6] Some are peptides, such as insulin, oxytocin, vasopressin and GnRH. [3]
• Endogenous. Made by the body itself, as incretin hormones are released from the intestine after nutrients arrive. [7]
• Neuropeptide. A peptide that acts as a signal in the nervous system; neuropeptides are thought to spread through the fluid between cells and act on nearby tissue. [8]
• Receptor. A large molecule, on a cell surface or inside a cell, involved in chemical signaling. [9]
• Ligand. Any molecule, including a drug, hormone or neurotransmitter, that binds to a receptor. [9]
• Agonist. A substance that activates a receptor to produce a response. [9]
• Antagonist. A substance that prevents receptor activation. [9] See agonists and antagonists.
• Selectivity. How much a drug acts on a given site compared with others. Few if any drugs act on only one receptor. [9]
• Incretin. A hormone released from the intestine after glucose or nutrients that stimulates insulin secretion. GLP-1 and GIP are the two incretin hormones. [7]
• GLP-1. Glucagon-like peptide-1, one of the two incretin hormones. [7] Medicines built on it are covered on the GLP-1 and GIP biology page.
• Protease (peptidase) and DPP-4. Enzymes that cut peptides and proteins. Dipeptidyl peptidase-4 cleaves the two end amino acids of GIP and GLP-1 in plasma and inactivates them. [7] See enzymes and peptide breakdown.

What the body does to a medicine

• Pharmacokinetics. What the body does to a drug: the movement of a drug into, through and out of the body. [10]
• Pharmacodynamics. What a drug does to the body, including receptor binding. [10]
• Bioavailability. The extent and rate at which the active part of a drug enters the bloodstream. [11] See bioavailability.
• Half-life. The time for a drug's level to fall by half; for first-order elimination, biologic half-life is 0.693 divided by the elimination rate constant. [10] One review describes natural peptides as often unstable, with a short half-life and fast elimination. [3]
• Clearance. The rate of drug elimination divided by the drug's concentration in plasma. [10]
• Volume of distribution. The amount of drug in the body divided by its plasma concentration. [10]
• Elimination. Removal of a drug from the body; most drugs and their metabolites leave through the kidneys in urine. [12]
• Bioequivalence and therapeutic equivalence. Bioequivalent products give equivalent drug concentrations in the same patient; therapeutically equivalent ones have the same therapeutic and adverse effects. [11]

Ingredients, names and products

• Active ingredient. The component that provides the drug's pharmacological activity or other direct effect. [13]
• Excipient. An added ingredient other than the active one, such as a color, flavor or preservative. Products with the same active ingredient may differ in excipients. [13]
• Dosage form. The physical form in which a drug is produced and dispensed, such as a tablet, a capsule or an injectable. [13]
• Formulation. The complete make-up of a product: active ingredient, excipients and dosage form. Bioavailability differences among formulations of the same drug can matter clinically. [11]
• Brand name. A proprietary, trademark-protected name for a drug. [13]
• Generic name (INN). The nonproprietary name of a substance. WHO's International Nonproprietary Names are unique, globally recognized and public property. [14]
• INCI name. The common ingredient name used for labeling cosmetics. [15] In the United States, cosmetic ingredients must be listed by common or usual names, generally in descending order of predominance. [16]
• Prescription drug product. A product that requires a doctor's authorization to purchase. [13]

Medicines, approval and compounding (United States)

• New drug application (NDA). The submission a sponsor makes to FDA once it believes enough evidence of safety and effectiveness has been obtained to meet FDA's marketing requirements. [13]
• Generic drug application (ANDA). An abbreviated application for a generic drug, which generally need not include animal and clinical data because the applicant shows the product is bioequivalent to the innovator drug. [13]
• Biologic license application (BLA). Biological products are approved under the Public Health Service Act. [13]
• Investigational new drug (IND). The route through which a sponsor obtains an exemption from the rule that a drug needs an approved application before it is shipped across state lines, so that an investigational drug can be sent to clinical investigators. [24]
• Off-label use. Unapproved use of an approved drug. Safe, to FDA, does not mean no side effects; it means the benefits for a particular use outweigh the risks. [25] See approved vs off-label vs investigational use.
• Compounding. Preparing a drug for an individual patient who cannot be treated with an FDA-approved medication, for example because of a dye allergy. Compounded drugs are not FDA-approved. [26] See compounded medicines.
• 503A and 503B (outsourcing facility). Sections of the federal law that cover compounding. Outsourcing facilities were created in 2013, and drugs they compound must meet current good manufacturing practice, whereas pharmacist or physician compounding under section 503A does not. [26]
• Public assessment report. A published account of how a regulator assessed a medicine: the European public assessment report (EPAR) from EMA, or the Public Assessment Report (PAR) from the UK's MHRA. [27][28]
• Warning letter. An FDA letter describing apparent violations; FDA notes the situation may have changed after the letter. [29]
• Prohibited List. The World Anti-Doping Agency's list of substances and methods prohibited in sport, updated at least annually. [30] See anti-doping rules for peptides.

Research design and evidence

• Preclinical study. Research before testing in people, of two types: in vitro and in vivo. [31] In vitro generally means work in cells or laboratory samples, in vivo means work in living animals.
• Clinical trial. A research study that tests how well new medical approaches work in people. Every trial has a protocol, or action plan. [32]
• Phase 1, 2 and 3. Phase 1 asks about safety and dosage, Phase 2 about efficacy and side effects, and Phase 3 about efficacy and monitoring of adverse reactions in larger groups. [33]
• Randomized, placebo-controlled trial. A trial in which volunteers are randomly assigned to the test treatment or to a placebo, an inactive substance that looks like the treatment. [34]
• Placebo effect. A beneficial health outcome resulting from a person's expectation that an intervention will help. [34]
• Blinding. Keeping participants or staff unaware of who receives which treatment. Lack of blinding can bias treatment-effect estimates. [35]
• Endpoint. What a trial measures as its outcome. [36]
• Clinical outcome. A direct measure of whether people feel or function better, or live longer. [36]
• Biomarker. A defined characteristic measured as an indicator of a biological process or response to treatment. It is not an assessment of how a person feels, functions or survives. [36][37]
• Surrogate endpoint. A measure used in place of a clinical outcome; extensive evidence is needed before it can be accepted as one. [36] See biomarker changes versus meaningful outcomes.
• Adverse event. Any undesirable experience associated with the use of a medical product. [38] A serious adverse event includes death, a life-threatening event, or hospitalization. [38]
• Systematic review. A study that identifies, appraises and synthesizes all the empirical evidence meeting pre-specified eligibility criteria to answer a specific question. [39]
• Meta-analysis. Combining results from individual studies into an overall statistic. It may be inappropriate if the studies are too different or of doubtful quality. [39]
• Publication bias. Statistically significant results being more likely to be fully reported than non-significant ones. [40]
• Retraction. A journal withdrawing an article because of pervasive error or unsubstantiated or irreproducible data. [41]
• Trial registry. A public database of studies. WHO's platform aims to give a complete view of research. [42]
• PubMed. A free index of more than 40 million biomedical citations and abstracts, without full-text articles. [43] See how to find peptide studies.