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Peptide

A peptide is any compound produced by amide formation between a carboxyl group of one amino acid and an amino group of another. This is the definition in the IUPAC-IUB recommendations on the nomenclature of amino acids and peptides, which add that the amide bonds in peptides may be called peptide bonds.[1]

What is an amino acid residue?

When two or more amino acids combine to form a peptide, the elements of water are removed, and what remains of each amino acid is called an amino-acid residue. The residue with a free, or at least not acylated, amino group is N-terminal; the residue with a free carboxyl group, or one that does not acylate another residue, is C-terminal.[1]

The N-terminal amino group need not be free: the recommendations note it may, for example, be acetylated or formylated. Likewise the C-terminal residue may acylate ammonia, giving a C-terminal amide. Residues are named from the trivial name of the amino acid, omitting the word acid from aspartic acid and glutamic acid.[1]

Where does a peptide end and a protein begin?

The same recommendations state that peptides with fewer than about 10-20 residues may be called oligopeptides and those with more, polypeptides. Polypeptides of specific sequence of more than about 50 residues are usually known as proteins, though authors differ greatly on where they start using that term.[1]

A 2014 review places peptides between classic small organic molecules and larger biomolecules such as proteins, and a 2021 review notes that synthetic peptides are relatively small compared with monoclonal antibodies and other proteins.[2],[3]

What are eupeptide and isopeptide bonds?

The word peptide usually applies to compounds whose amide bonds form between C-1 of one amino acid and N-2 of another, sometimes called eupeptide bonds, but it includes compounds with residues linked by other amide bonds, sometimes called isopeptide bonds.[1]

How are synthetic peptides made?

Merrifield described solid phase peptide synthesis in 1963, with the synthesis of a tetrapeptide.[4]

A 2014 review states that most peptides today are manufactured by solid-phase peptide synthesis (SPPS), and describes the impurity types associated with it. Amino acid deletions and insertions are related to inefficient Fmoc-deprotection and to excess use of amino acid reagents, respectively.[2]

How is a synthetic peptide characterized?

Synthetic peptides are subject to structural modifications from starting materials, the manufacturing process and storage conditions, and liquid chromatography-mass spectrometry is used to characterize them. The same review discusses thresholds for identifying and controlling impurities based on available regulatory guidance.[3]

HPLC in size-exclusion, ion-exchange and reversed-phase modes is used for peptide separation and analysis.[5]

ICH Q6B notes that amino acid composition analysis provides useful structural information for peptides and small proteins, but is generally less definitive for large proteins.[6]

Limitations

The size boundaries between oligopeptide, polypeptide and protein are conventions, not sharp chemical limits; the IUPAC-IUB text itself says authors differ on where the term protein starts.[1]

Being a peptide says nothing about a compound's biological activity or regulatory status. Those are described, where sourced, on individual compound pages.

Compound profiles

Compound profiles whose identity section records the sequence and molecular formula that an identity result is compared against.

References

  1. IUPAC-IUB Joint Commission on Biochemical Nomenclature. Nomenclature and symbolism for amino acids and peptides. Recommendations 1983. Biochem J. 1984;219(2):345-373 (section 3AA-11). PMID 6743224 · DOI 10.1042/bj2190345 · PMC1153490
  2. D'Hondt M, Bracke N, Taevernier L, et al. Related impurities in peptide medicines. J Pharm Biomed Anal. 2014;101:2-30. PMID 25044089 · DOI 10.1016/j.jpba.2014.06.012
  3. Lian Z, Wang N, Tian Y, Huang L. Characterization of Synthetic Peptide Therapeutics Using Liquid Chromatography-Mass Spectrometry: Challenges, Solutions, Pitfalls, and Future Perspectives. J Am Soc Mass Spectrom. 2021;32(8):1852-1860. PMID 34110145 · DOI 10.1021/jasms.0c00479
  4. Merrifield RB. Solid Phase Peptide Synthesis. I. The Synthesis of a Tetrapeptide. J Am Chem Soc. 1963;85(14):2149-2154. DOI 10.1021/ja00897a025
  5. Mant CT, Chen Y, Yan Z, et al. HPLC analysis and purification of peptides. Methods Mol Biol. 2007;386:3-55. PMID 18604941 · DOI 10.1007/978-1-59745-430-8_1 · PMC7119934
  6. ICH Q6B Specifications: Test Procedures and Acceptance Criteria for Biotechnological/Biological Products. U.S. FDA guidance for industry, August 1999. FDA docket FDA-1998-D-0003