TY - JOUR

T1 - On-resin N-formylation of peptides: a head-to-head comparison of reagents in solid-phase synthesis of ligands for formyl peptide receptors

AU - Christensen, Simon Bendt

AU - Hansen, Anna Mette

AU - Franzyk, Henrik

PY - 2017

Y1 - 2017

N2 - 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, lmost 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 andversatile 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.

AB - 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, lmost 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 andversatile 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.

U2 - 10.1002/psc.2998

DO - 10.1002/psc.2998

M3 - Journal article

C2 - 28421689

VL - 23

SP - 410

EP - 415

JO - Journal of Peptide Science

JF - Journal of Peptide Science

SN - 1075-2617

IS - 5

ER -