The chemical ligation of selectively S-acylated cysteine peptides to form native peptides via 5-, 11- and 14-membered cyclic transition states

Alan R. Katritzky, Nader E. Abo-Dya, Srinivasa R. Tala, Zakaria K. Abdel-Samii

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Cysteine and C-terminal cysteine peptides are selectively S-acylated at 0-20 °C by N-(Pg-α-aminoacyl)benzotriazoles to give N-Pg-S-acyl-isodi-, -isotri-, and -isotetra-peptides isolated in good yields. N-Fmoc-S-acyl-isopeptides are Fmoc deprotected to afford free S-acyl-isopeptides isolated in high yields. S-Acyl-isodi-, S-acyl-isotetra-, and S-acyl-isopenta-peptides undergo chemical ligation; migration of the cysteine S-acyl groups to the N-terminal amino acids via 5-, 11-, and 14-membered transition states giving the corresponding native di-, tetra-, and penta-peptides. By contrast, the S-acyl-isotripeptide prefers intermolecular acylation from one molecule to another over an 8-membered intramolecular transition state. The developed methodology allows convenient isolation of stable, unprotected S-acyl cysteine peptides including the first isolation of S-acyl-isopeptides, which should facilitate the investigation of ligation by physical organic chemistry techniques.

Original languageEnglish (US)
Pages (from-to)2316-2319
Number of pages4
JournalOrganic and Biomolecular Chemistry
Volume8
Issue number10
DOIs
StatePublished - May 21 2010

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