Poster Presentation International Peptide Symposium 2023

Synergistic n→π* and nN→π*Ar Interaction in Controlling Polyproline Conformation with C-terminus Modification (#228)

Paramesh Das 1 , Jugal Kishore Rai Deka 1 , Bani Kanta Sarma 1
  1. Jawaharlal Nehru Centre for Advanced Scientific Research, Bengaluru, India, Bengaluru, KARNATAKA, India

Carbonyl-carbonyl (CO···CO) n→π* interaction often coexists with hydrogen bond or another n→π* interaction. However, cooperativity of n→π* interactions with other interactions or among themselves is not studied. Herein, we have synthesized a set of proline-diacylhydrazine (Pro-DAH) hybrid molecules and established a synergistic relationship between n→π* interaction in their Pro side and nN→π*Ar interaction in the DAH side by 1D, 2D NMR and theoretical studies.1 Wennemers and coworkers showed that hydrogen bond donors at the γ-position (S-chirality) of the proline ring polarized the C-terminal CO via hydrogen bonding, which enhanced CO···CO interaction from the N- to C-terminal CO leading to trans proline stabilization.2 When such a modified proline was incorporated in an oligo-Pro, it stabilized all-trans amide in PPII helix. These studies inspired us to study the effect of incorporating a DAH unit at the C-terminus of an oligo-Pro. We observed that these peptides adopted all-trans amide polyproline II (PPII) helical conformations in propanol as well as aqueous medium. This is unusual as propanol is known to stabilize oligo-Pro in all-cis amide PPI structure. We propose that this synergistic n→π* and nN→π*Ar interactions at the C-termini of these oligo-Pro induced cooperative CO···CO interactions by polarizing neighboring CO groups that enforced all the proline rings to be locked in trans conformation. As a result, this cascade effect or domino effect of n → π* interactions from the C-terminus to the N-terminus enforces the overall stabilization of polyproline in PPII helical geometry. Our study indicates that just by controlling the amide geometry of the C-terminal Proline, we can control the secondary structure of a proline oligomer.

 

  1. References: 1) Deka, J. K. R.; Borah. D.; Das, P.; Sahariah, B; Vishnoi, P.; Sarma, B. K. Synergistic n→π* and nN→π*Ar interactions in C-terminal modified prolines: Effect on Xaa-Pro cis/trans equilibrium. Chem. Commun., 2023, 59, 6080–6083. 2) Kuemin, M.; Nagel, Y. A.; Schweizer, S.; Monnard, F. W.; Ochsenfeld, C.; Wennemers, H. Tuning the cis/trans conformer ratio of Xaa-Pro amide bonds by intramolecular hydrogen bonds: the effect on PPII helix stability. Angew. Chem. Int. Ed. 2010, 49, 6324–6327.