Synthesis and structural and biological studies of efrapeptin C analogues

Abstract

A series of analogues of efrapeptin C (1), with variations in the central tripeptide epitope (positions 6-8), prepared by a combination of solid- and solution-phase peptide syntheses. The conformations of the modified compounds 2-6 were investigated by circular-dichroism (CD) spectroscopy to differentiate between 310- and α-helical secondary structures. The inhibitory activities of the new compounds towards F1-ATPase from E. coli were determined. The modified congeners 3-5 were less active by one order of magnitude compared to 1 (Ki 10 μM), and 6 was completely inactive. Our experiments demonstrate that the flexible, central tripeptide epitope, comprising positions 6-8 in 1, is crucial for molecular recognition, even slight sequence modifications being hardly tolerated. © 2007 Verlag Helvetica Chimica Acta AG, Zürich.