Effects of end group and aggregation on helix conformation: crystal structure of Ac-(Aib-Val-Ala-Leu)2-Aib-OMe

The role of end groups in determining stereochemistry and packing in hydrophobic helical peptides has been investigated using an alpha-aminosobutyric acid (Aib) containing model nonapeptide sequence. In contrast to the Boc-analogue, Ac-(Aib-Val-Ala-Leu)2-Aib-OMe crystallizes with two independent molecules in a triclinic cell. The cell parameters are: space group P1, a = 10.100(2)A, b = 15.194(4)A, c = 19.948(5)A, alpha = 63.12(2) degrees, beta = 88.03(2) degrees, y = 88.16(2) degrees, Z = 2, R = 7.96% for 5140 data where magnitude of Fo > 3 rho(F). The two independent molecules alternate in infinite columns formed by head-to-tail hydrogen bonding. The helices in the two independent molecules are quite similar to each other but one molecule is rotated approximately 123 degrees about its helix axis with respect to the other. All the helical columns pack parallel to each other in the crystal. Replacement of the bulky Boc group does not lead to any major changes in conformation. Packing characteristics are also similar to those observed for similar helical peptides.