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Custom peptide synthesis (revision 4)

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Custom peptide synthesis
InputA sequence and a specification
Priced byLength, scale, purity grade, modifications
Contrast withCatalogue supply of stocked compounds
Topic infobox · conventions

Custom peptide synthesis is the manufacture of a peptide to a sequence and specification supplied by the customer, as distinct from supply of a catalogue item held in stock. It is the ordinary route by which research peptides that are not commercially stocked are obtained.[1]

A custom order is defined by more than a sequence. Scale, purity grade, C-terminal functionality, any modifications such as acylation or cyclisation, salt form, and which determinations will appear on the certificate are all specification items, and a quotation that does not enumerate them is quoting for an underdetermined thing.[2]

What a specification should fix

[edit]
ItemWhy it matters
Sequence and modificationsDefines the molecule; ambiguity here is fatal
C-terminal formAcid or amide; set by linker choice
Purity gradeDetermines purification effort and price
Salt formTrifluoroacetate counterion or exchanged; affects Peptide content
ScaleNet peptide mass, not solid mass
Determinations on the certificateWhat will actually be reported

The distinction between net peptide mass and solid mass is the one most often left ambiguous. An order for "10 mg" may be filled as 10 mg of solid, which at typical content is rather less peptide, or as solid containing 10 mg of peptide. The two differ by the counterion and water fractions.[2]

Sequence ambiguity is the failure with the largest consequence. One-letter and three-letter codes, D-residue conventions, and non-standard abbreviations for modified residues all vary between houses, and a sequence should be unambiguous on its face. See Peptide.

References

  1. ^ Behrendt R, White P, Offer J. "Advances in Fmoc solid-phase peptide synthesis." Journal of Peptide Science 22(1):4–27 (2016). PMID 26785684.
  2. ^ a b United States Pharmacopeia, General Chapter <1503>, Quality Attributes of Synthetic Peptide Drug Substances.