Depsipeptides, linear, conformations

Proline has long been known to help a peptide adopt a reverse-turn conformation (71). For example, the classic type VI turn was defined as having a cm-amide bond between residues i + 1 and i + 2, which proline facilitates in the i + 2 position due to its disubstituted amide nitrogen. The sequence d-Pro-l-Pro in particular has been found to adopt a reverse-turn conformation (84-86) and alternating d/l amino acid sequences facilitate cycli-zation of small peptides as discussed in a review of cyclization of peptides and depsipeptides by Davies (87). Particular difficulties in cyclization of linear tetrapeptides containing residues of the same chirality have been found (88). Durani has discussed designing small folded proteins based on an alphabet of d- and L-amino acids (89). 

Linear depsipeptides such as Z-LHyv-oMeLeu-OtBu (Pletnev et a/., 1977b), LVal-LHyv (Galitsky et aL, 1977), and oMeVal-oHyv (Pletnev et ai, 1977a) have extended conformations similar to those observed for the di-and tripeptides. 

Peptides with type II loops containing 4 - 1 hydrogen bonds are listed in Table IV. This type of conformation has occurred predominantly for ld, dl, L,Gly, and Gly,L sequences in cyclic and linear peptides and depsipeptides. The one exception noted so far is the 4 - 1 loop in Ibu-LPro-LAla-NHiPr, which is identical to the one occurring in Ibu-LPro-oAla-NH/Pr. The values for the conformational angles [Pg.47]

The most stable conformation of cyclic depsipeptides appears to be a boat or twist-boat conformation [17, 18]. Hydrogen bond formation in the twist-boat conformation may stabilize the 2,5-morpholinediones, and likely contributes to ring stability. This has been attributed to the high trans-ds barrier for the nonalkyl-ated amide bond. In order to form the cyclic compounds, the linear precursors should adopt a folded conformation with a as amide bond, rather than the more extended and favored trans amide bond. Thus, rather drastic conditions are required for the formation of 2,5-morpholinedione derivatives [19]. 

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