CONFORMATIONS OF CYCLIC HEPTAPEPTIDES - CRYSTAL-STRUCTURE AND COMPUTATIONAL STUDIES OF EVOLIDINE

Evolidine, cyclo(Ser-Phe-Leu-Pro-Val-Asn-Leu), crystallized as a tetrahydrate from aqueous ethanol in a triclinic cell of dimensions alpha = 11.370 (3) angstrom, b = 11.705 (4) angstrom, c = 9.058 (6) angstrom, alpha = 94.56 (7)degrees, beta = 111.50 (5)degrees, gamma = 73.23 (2)degrees with one formula unit in space group P1. Least-squares refinement of 3484 observed data (I > 3-sigma(I)) led to residuals R = 0.054 and R(w) = 0.061. The cyclic heptapeptide backbone includes two beta-turns, one of type I at Leu-Ser and one of type VI(a), which incorporates a cis peptide bond, at Leu-Pro. Transannular backbone hydrogen bonds occur between Phe N-H and Asn C'= O and between Phe C'= O and both Val N-H and Asn N-H. This structure corresponds to the minimal version of a classical beta-bulge as identified in proteins. The backbone conformation is close to that proposed from solution NMR data of evolidine (Kopple, K. D. Biopolymers 1971, 10, 1139; Peishoff, C. E.; Bean, J. W.; Kopple, K. D. J. Am. Chem. Soc., following paper in this issue) and parallels that from both a crystal structure of the heptapeptide ilamycin, which has a different sequence, and the proposed solution conformation of a third cyclic heptapeptide containing no N-alkylated residues. These parallels, together with computations, suggest that the two beta-turn backbone incorporating a bulge can be a favorable motif for cyclic heptapeptides.