Differences in hydration and association of helical Boc-Val-Ala-Leu-Aib-Val-Ala-Leu-(Val-Ala-Leu-Aib)2-OMe.xH2O in two crystalline polymorphs

J Med Chem. 1992 Oct 16;35(21):3885-9. doi: 10.1021/jm00099a016.

Abstract

The 15-residue apolar peptide, Boc-Val-Ala-Leu-Aib-Val-Ala-Leu-(Val-Ala-Leu-Aib)2-OMe has been crystallized from 2-propanol-water (form I). The crystal parameters for I are as follows: C74H133N15O18.2H2O, space group P2(1), a = 9.185 (6) A, b = 47.410 (3) A, c = 10.325 (9) A, beta = 91.47 (2) degrees, Z = 2, R = 6.3% for 4532 reflections observed > 3 sigma (F), resolution 0.94 A. The structure is almost completely alpha-helical with eleven 5-->1 hydrogen bonds and one 4-->1 hydrogen bond near the N-terminus. The structure has been compared with a polymorph (form II) obtained from methanol-water (Karle, I. L.; Flippen-Anderson, J. L.; Uma, K.; Sukumar, M.; Balaram, P., J. Am. Chem. Soc. 1990, 112, 9350-9356). The two forms differ in the extent of hydration; form I contains two water molecules in the head-to-tail region of helical columns, while form II is more extensively solvated, with the equivalent of 7.5 water molecules. The three-dimensional packing of helices is completely parallel in I and antiparallel in II.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Models, Molecular
  • Molecular Sequence Data
  • Peptides / chemistry*
  • Protein Conformation
  • Water / chemistry
  • X-Ray Diffraction

Substances

  • Peptides
  • Water
  • N-tert-butyloxycarbonyl-valyl-alanyl-leucyl-aminoisobutyryl-valyl-alanyl-leucyl(valyl-alanyl-leucyl-aminoisobutyryl)(2) methyl ester