On ‐resin N‐formylation of peptides: a head‐to‐head comparison of reagents in solid‐phase synthesis of ligands for formyl peptide receptors

General conditions for efficient on‐resin N‐formylation of peptides were identified by screening of a number of reagents comprising aliphatic formates (ethyl formate, 2,2,2‐trifluoroethyl formate, and cyanomethyl formate), aromatic esters (phenyl formate and p‐nitrophenyl formate), and N‐formylimidazole and in situ activation of formic acid with the coupling reagent 1‐ethyl‐3‐(3‐dimethylaminopropyl)carbodiimide. Initially, reaction time and influence of solvent were examined for the formylation of a short model peptide. The most efficient reagents were examined further by using different linkers and solid supports in the synthesis of an array of longer formyl peptide ligands. For p‐nitrophenyl formate and N‐formylimidazole, almost complete conversion was reached within 2 h, albeit longer peptides attached to Tentagel resins via different linkers required an extended reaction time. Overall, the commercially available activated ester p‐nitrophenyl formate proved to be most convenient and versatile as high formylation degrees were obtained after 1–3 h at room temperature, while either conventional or microwave‐assisted heating allowed reduction of the formylation time to 20 min. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

4‐Nitrophenyl formate was found to be the most convenient reagent in solid‐phase formylation of peptides with a high formylation degree within 20 min to 3 h depending on reaction temperature a...

Source: Journal of Peptide Science - April 19, 2017 Category: Biochemistry Authors: Simon Bendt Christensen, Anna Mette Hansen, Henrik Franzyk Tags: Research Article Source Type: research