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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1994 Jul 5;91(14):6584–6588. doi: 10.1073/pnas.91.14.6584

Peptide segment ligation strategy without use of protecting groups.

C F Liu 1, J P Tam 1
PMCID: PMC44247  PMID: 8022823

Abstract

We describe the concept and the verification of a chemical ligation approach to the synthesis of proteins using peptide segments with no protecting groups and no activation of the C-terminal alpha-carboxyl group. This approach consists of three steps: (i) aldehyde introduction, in which a masked glycolaldehyde ester is linked to the carboxyl terminus of an unprotected peptide by reverse proteolysis; (ii) ring formation, in which the unmasked aldehyde reacts with the N-terminal alpha-amino group of the second unprotected peptide containing either a cysteine or a threonine residue to form a thiazolidine or oxazolidine ring at an acidic pH; and (iii) rearrangement in which O-acyl ester linkage is transferred to N-acyl amide linkage to form a peptide bond with a pseudoproline structure at higher pH. The feasibility of this scheme was verified by a model study on small compounds and its potential was demonstrated by the synthesis of a 50-residue epidermal growth factor-like peptide containing a preformed disulfide bond.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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