Conformational investigations of cyclic dipeptides: Cyclo‐glycyl‐L‐methionyl, cyclo‐glycyl‐D,L‐norleucyl and cyclo‐glycyl‐D,L‐norvalyl

Abstract

In order to elucidate the possible influence that the intramolecular interaction between the side-chain thioether group and the adjacent amide bond may have on the conformational equilibria in sulphurcontaining amino acid residues, we recently investigated,' by means of 'H NMR, a series of linear model compounds-methyl esters and N'-methylamides of N-acetyl-S-methylcysteine, N-acetylmethionine, Nacetylnorvaline and N-acetylnorleucine. We found no differences in the conformational equilibria with the methionine and norleucine derivatives. Only minor differences were observed in the N-Ac-(S-Me)Cys-NHCH, and N-Ac-Nvl-NHCH, pairs.Similar investigations have now been performed with more rigid models, viz. the cyclic dipeptides'H NMR measurements were performed in deuteriated methanol in the temperature range 210-290K. Spectra were recorded at 2 0 K intervals and analysed by means of the procedure described in Ref. 1. RESULTS AND DISCUSSION The conformation of DKPringsThe boat conformation should be expected in the case of diketopiperazine (DKP) rings of cyclic dipeptides of the general formula c-Gly-X (X =the amino acid residue with side-chain R) of the two boat forms shown in Fig. 1, the one with a pseudoaxial orientation of the side-chain R dominates in the equilibrium.* The average boat conformation of the DKP rings can be described by the ~a r a m e t e r ,~ which expresses the degree of ring puckering. Its relationship to the conformational angles 4 and JI in the amino acid residues