Conformational change in the thiazole and oxazoline containing cyclic octapeptides, the patellamides. Part 1. Cu2+ and Zn2+ induced conformational changeElectronic supplementary information (ESI) available: further calculational details. See http://www.rsc.org/suppdata/p2/b2/b201823n/

Abstract

Conformational change during the binding of Cu2+ and Zn2+ to the thiazole and oxazoline containing cyclic octapeptides, the patellamides, is examined by a combination of experimental and theoretical methods. Circular dichroism and NOE-restrained molecular dynamics studies indicate that upon complexing with one equivalent of Cu2+, patellamide C undergoes a change in conformation which pre-organises a second Cu2+ binding site, and that the binding of a second Cu2+ induces no further conformational change. The binding of Zn2+ induces little conformational change in patellamide C. A restrained conformational search shows that the conformational change induced by the addition of one equivalent of Cu2+ to patellamide C is an intrinsic design feature of the system. Electronic structure calculations indicate that the patellamides provide an ideal coordination environment for Cu2+. On the basis of the evidence gathered, it can be proposed that Cu2+ is the biologically relevant metal for the patellamides.