Antiparallel pleated beta-sheets observed in crystal structures of N,N-bis(trichloroacetyl) and N,N-bis(m-bromobenzoyl) gramicidin S

Despite intensive efforts, the structures of gramicidin S (GS) [cyclo(-Val- Orn-Leu-D-Phe-Pro-)(2)] and its analogues have not been elucidated by the X -ray diffraction method, except for the GS-urea complex (Hull et al., Natur e 275, 206-207, 1978; Tishchenko et al., Acta Cryst. D53, 151-159, 1997). W e focused on the acetylation of GS to obtain suitable crystals for X-ray di ffraction. The amino groups of Orn residues were capped with trichloroaceti c and m-bromobenzoic acids. Both trichloroacetyl and m-bromobenzoyl GSs (Tc GS and BzGS, respectively) are hydrophobic and their properties are similar to those of acetyl-GS (AcGS). Although it is well known that AcGS yields h exagonal crystals, TcGS and BzGS yield monoclinic and orthorhombic crystals in aqueous dimethylformamide solution, respectively. Their cell volumes we re approximately one-fourth or one-eighth of the hexagonal cell volume. The crystal structures of TcGS and BzGS were determined as the first examples of acetylated GS analogues: TcGS, C64H00N12O12Cl6 . 3(C8H7NO), M-r = 1651.4 7, monoclinic, P2(1), a = 15.4366(6) Angstrom, b = 18.5312(4) Angstrom, c 1 6.4774(6) Angstrom, beta = 14.160(2)degrees, V = 4300.6(2) Angstrom (3), Z = 2; and BzGS, C64H98N12O12Br2 . 1.54(H2O), M-r = 1535.21, orthorhombic, P2 (1)2(1)2(1), a = 16.748(10) Angstrom, b = 18.834(5) Angstrom, c = 28.558(10 ) Angstrom, V = 9008(7) Angstrom (3), Z = 4. Both these peptide molecules f ormed an antiparallel pleated beta -sheet, and pseudo twofold symmetries ex isted in the repeated sequence. beta -Turns formed at the fragments Of D-Ph e-Pro were classified into type IF based on their characteristics. The pept ide conformations of TcGS and BzGS were similar to each other, and these st ructural features agreed with those of structures proposed by the previous studies. (C) 2001 Academic Press.