STUDY OF beta-SHEET HELIX INTERACTIONS BASED ON CONFORMATIONAL PROPERTIES OF SYNTHETIC D,L-ALTERNATING DECAPEPTIDES

De novo peptide design is based on the ability to construct peptide sequences with predictable folding patterns. Helices and beta-sheet have been the focus of considerable synthetic attention in attempts to assemble mimics for helical bundles and all beta-motifs. In contrast, strategies for construction of beta-sheet helix have been less widely explored. The ?-sheet helical architecture is constructed from polypeptides that are coiled into a large helix, formed by stacks of ?-sheets separated by loops. beta-Sheet helices are present in the fibrous form of transyretin, that play an important role in bovine spongiform encephalopathy (BSE) and form the crucial structural elements in insect antifreeze proteins. We report on synthetic analogues able to form ?-sheet helices and on the structural comparison with ?-helices formed by D,L-alternating peptides. Alternating D,L peptides are able to assume very specific conformations, including, among others, various kinds of single and double stranded ?-helical structures. ?-Helix conformations share an important number of structural features with ?-sheet ones, as a set of hydrogen bonds between amino and carbonyl backbone groups and ?L, ?L,?D, and ?D values in poly-L- and poly-D-peptides. Double stranded ?-helices, both parallel and antiparallel, are stabilized by systematic interchain NH-CO hydrogen bonds between adjacent peptide chains and by intrachain hydrogen bonds equivalent in pairs. They are symmetrical structures in which the backbone CO and NH groups are oriented quasi-parallel to the helical axis but in alternating opposite directions. The side chains are oriented perpendicular to the helical axis on the outside of the helix. Insertion of proline residues within a homochiral segment has been used to nucleate ?-sheet helical conformation. The juxtaposition of proline within repetitive motifs supports the formation of ?-turns which are labile and impart dynamic and flexibility upon sliding between successive Pro-containing repeats. Furthermore, the periodicity with which Pro and Xaa amino acid are arranged with the peptide directs the formation of specific secondary structures. We have observed -XPXPXPXP- periodicity with the synthetic homologous of ?-casomorphin-8 and a -PXXP- periodicity using a synthetic, homochiral sequence having X=F with 13 amino acid. Here we report about synthesis and conformational behaviour of both peptides. References [1] Nowick J.S. Acc. Chem. Res. (2008) 41(10),1319-1330 [2] O'Neil K.T., DeGrado W.F., Science (1990) 250, 646-651 [3] Lorenzi G.P., Gerber C., Jackle H., Macromolecules (1985) 18, 154-159