Synthesis and characterization of highly structured pentapeptides containing dipropylglycine

ORGN 672

Jia Wang, jwang9@lsu.edu and Robert P. Hammer, rphammer@lsu.edu. Department of Chemistry, Louisiana State University, 232 Choppin Hall, Baton Rouge, LA 70803
Cα,α disubstituted amino acids (ααAAs) are widely utilized to conformationally constrain peptides. Several pentapeptides containing dipropylglycine (Dpg) at alternating positions and their unconstrained L-norvaline (Nva) analogues were synthesized to fully investigate the impact of Dpg on peptide backbone structure in a biocompatible aqueous solution. CD and NMR spectral analysis suggest that Dpg containing peptides adopt more ordered structures relative to their Nva containing analogues. The effects of the central residues (Ala, Thr, Tyr, Val) and the salt bridge effect resulting from Glu and Lys play important roles in the peptide conformation. The peptide Ac-Glu-Dpg-Tyr-Dpg-Lys-NH2 adopts a 310-helical conformation which is stabilized by i→i+3 hydrogen bonding between the acetyl carbonyl and the Tyr NH and between Glu carbonyl and the Dpg4 NH. The conformation of Ac-Glu-Dpg-Tyr-Dpg-Lys-NH2 consistent with ROE distances was confirmed through molecular dynamics and energy minimization methods.