Conformation of Antamanide

The conformation of the cyclic decapeptide antamanide (1) in CDCl₃ solution was determined by means of NMR‐spectroscopic methods. Distances obtained from 40 negative NOE values at 500 MHz at low temperature were used as constraints in calculations with the GROMOS molecular dynamics program package to elucidate the most stable backbone conformation in solution. It turned out that there is a fast conformational equilibrium between up to four conformations which differ in a flip about φ and ψ around the two amide bonds Ala⁴–Phe⁵ and Phe⁹–Phe¹⁰. Side chain conformations were determined using homo‐ and heteronuclear coupling constants. Carbon relaxation times provide information about the internal flexibility of 1. Three new antamanide derivatives in which Pro³, Pro⁷, or Pro⁸ have been substituted by γ‐thiaproline (Thz) were synthesized and crystallized from acetone/water. The X‐ray analyses of these Thz derivatives demonstrate that in the presence of water antamanide adopts a preferred structure which includes four water molecules for building up a compact hydrogen‐bonded structure, which differs from the conformation in chloroform sulution.