PeptidePedia The community reference

Peptide (revision 10)

Old revision·14:32, 9 Sep 2024·CDMO_Caradoc

This is an old revision of this page, as it stood at 14:32, 9 Sep 2024, saved by CDMO_Caradoc with the summary attribute the stability figure to the study and its duration. It may differ substantially from the current revision, and any error it contains may since have been corrected.
Peptide
HAEGTFTSDVSSN-terminusC-terminus
Amino acid residues joined by amide bonds between a carboxyl and an amino group.
BondAmide (peptide) bond, C(=O)–NH
Conventional upper limit≈50 residues, above which "protein" is used
DirectionalityWritten N-terminus to C-terminus
Topic infobox · conventions

A peptide is a molecule composed of amino acid residues joined by amide bonds formed between the carboxyl group of one residue and the amino group of the next. The boundary with protein is conventional rather than physical; a common cut is around fifty residues, and regulatory definitions differ from chemical usage.[1]

Peptides are directional. By convention a sequence is written from the free amino terminus to the free carboxyl terminus, and the direction is not arbitrary: the same residues in reverse order are a different molecule with different properties. This is the reason a sequence given without its direction is ambiguous.[1]

Almost everything else on this wiki is a peptide or is about peptides — their synthesis, their analysis, their handling and their supply. Peptides sold for laboratory research are not approved for human use, whatever their sequence resembles; see Research use only.

Structure

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The amide bond has partial double-bond character, which restricts rotation and makes the six atoms of the peptide unit approximately planar. Conformational freedom therefore resides in the two dihedral angles either side of each α-carbon, and it is the accessible combinations of these that give rise to the α-helix, the β-sheet and the turn.[1]

Peptides of fewer than about fifteen residues are usually conformationally disordered in solution, sampling many states; longer chains can adopt a persistent fold. Several of the therapeutic peptides discussed on this wiki are helical over part of their length when bound to their receptor but substantially disordered when free, which matters for how they are analysed and stored.

Side chains determine chemistry. Charged residues set the isoelectric point and therefore the pH of minimum solubility; hydrophobic residues drive aggregation; asparagine, glutamine and methionine introduce the specific chemical liabilities discussed at Deamidation and Methionine oxidation.

Nomenclature and notation

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NotationMeaning
Three-letter codeAla, Gly, Lys — used for readability
One-letter codeA, G, K — used for long sequences
Lower-case letterD-amino acid, in some conventions
Aibα-aminoisobutyric acid, a common non-proteinogenic residue
NumberingFrom the N-terminus of the mature peptide unless stated

Numbering is a frequent source of confusion in the incretin literature, because GLP-1 is numbered from the N-terminus of proglucagon-derived GLP-1(1–37) while its active form begins at residue 7. The same substitution is therefore described as being at position 2 or position 8 depending on convention, which is why semaglutide is described both as having Aib at position 8 and as having a substitution at the second residue of the active peptide.[1]

References

  1. ^ a b c d International Union of Pure and Applied Chemistry and International Union of Biochemistry, Nomenclature and Symbolism for Amino Acids and Peptides (recommendations 1983; revised).