Link to Pubmed [PMID] – 3312053
Int. J. Pept. Protein Res. 1987 Jul;30(1):44-53
The conformational behaviour of pepstatin (Iva-Val-Val-Sta-Ala-Sta) and of two derived renin inhibitors, Boc-Phe-Nle-Sta-Ala-Sta-OMe, 1, and Boc-Phe-Nle-X-Ala-Sta-OMe, 2 (X = -NH-CH(iPr)-CHOH-CH2-CO-) was assessed in DMSO-d6 at various temperatures and in deuteriopyridine at -35 degrees. Complete assignment of almost all proton signals was achieved by 2D COSY, 2D NOESY and selective NOE experiments. The three compounds show similar extended conformations in both solvents, with the hydrophobic lateral chains extending away from the peptide backbone. In the case of pepstatin the solvated conformation is closely related to the structure found in the crystal of the pepstatin-Rhizopus chinensis complex. Strong NOE effects and precise determination of vicinal coupling constants show the lack of large structural differences between 1 and 2 at the level of the internal Sta or X residues, which are assumed to interact with the aspartyl residues of the renin active-site. This suggests that the 100-fold lower inhibitory potency of 2 is mainly due to unfavorable close contacts of the beta-branched residue X with constituent amino acids of the enzyme.