Designed beta-hairpin peptides with defined tight turn stereochemistry

The conformational analysis of two synthetic octapeptides. Boc-Leu-Val-Val- D-Pro-L-Ala-Leu-Val-Val-OMe (1) and Boc-Leu-Val-Val-D-Pro-D-Ala-Leu-Val-Val -OMe (2) has been carried our in order to investigate the effect of beta -t urn stereochemistry on designed beta -hairpin structures. Five hundred mega hertz H-1 NMR studies establish that both peptides 1 and 2 adopt predominan tly beta -hairpin conformations in methanol solution. Specific nuclear Over hauser effects provide evidence for a type II' beta -turn conformation for the D-Pro-L-Ala segment in I, while the NMR data suggest that the type I' D -Pro-D-Ala beta -turn conformation predominates in peptide 2. Evidence for a minor conformation in peptide 2, in slow. exchange on the NMR time scale. is also presented. Interstrand registry is demonstrated in both peptides 1 and 2. The crystal structure of 1 reveals two independent molecules in the crystallographic asymmetric unit. both of which adopt beta -hairpin confor mations nucleated by D-Pro-L-Ala type II' beta -turns and are stabilized by three cross-strand hydrogen bonds. CD spectra for peptides 1 and 2 show. m arked differences, presumably as a consequence of the superposition of spec tral bands arising from both beta -turn and beta -strand conformations. (C) 2001 John Wiley & Sons, Inc.*