Synthesis and conformational study of bioactive sequences containing a beta-turn element.

Four residues making almost a complete 180° turn in the direction of the peptide chain define a reverse turn, a common motif and recognition site in proteins. Hydrogen bonding interaction between residues i and i+3 and incorporation of Xxx-Pro (or Pro-Xxx) in the i+1 and i+2 positions are used to constrain a peptide to a revers-turn conformation. Reverse turns are common motifs and recognition sites in proteins. Receptor recognition, substrate specificity, and catalytic function generally reside in these loop regions that often connect residues of the ?-helices and ?-strands contributing to the structural stability of proteins (polypeptides). ?-turn, the most common type of reverse turn comprised of four residues, are characterized by ? and ? torsion angles of the i+1 and i+2 residues. The classical ?-turn is stabilized by an intramolecular hydrogen bond between the carbonyl oxygen of residue i and the amide hydrogen of residue i+3, although this is not an essential feature of reverse turns common in proteins Literature data show that turn sequences strongly dictates the preferred conformation and the strand alignment, cross-strand interaction and subsequently conformational stability are dictated by specificity of the turn. On these basis we have synthesized following, conventionally protected, bioactive sequences: Boc-Tyr-Pro-Phe-Pro-OMe; Boc-Tyr-Pro-Phe-Phe-OMe; Boc-Tyr-Pro-Phe-Trp-OMe; Boc-Pro-Phe-Pro-Phe-OMe; Boc-Pro-Phe-Pro-Phe-Val-OMe; Boc-Pro-Phe-Phe-Pro-OMe; Boc-Pro-Phe-Phe-Pro-Phe-Phe-OMe; Boc-Leu-Val-Val-Phe-Pro-OMe, Boc-Pro-Phe-Ile-Leu-OMe The main goal of this study is to examine the conformational preferences of the synthesized sequences and to explore the structural and functional diversity.