O‧‧‧C═O interaction, its occurrence and implications for protein structure and folding

Abstract

Various noncovalent interactions, long and short range, stabilize the native protein structure. We had observed a short‐range interaction between two adjacent peptide groups in a nearly perpendicular orientation through the involvement of an NH‧‧‧N hydrogen bond. Here we show that the other half of the peptide group, namely the carbonyl moiety, can also be involved through the O‧‧‧C═O interaction. Considering the interacting residues, the second residue of the pair has distinct backbone conformational angles, occurring in four clusters, each engendering well‐defined structural motifs. One of the motifs is the γ‐turn, another being polyproline II helix. The interacting pair is found mostly in the irregular region in protein structures, and the propensities of residues and the identification of the nearest secondary structure show interesting patterns. The most conspicuous β‐turn conformation is built from two consecutive γ‐turns, with embedded O‧‧‧C═O and NH‧‧‧N interactions, and there is considerable match of the residue usage at the central positions of the β‐turn and the γ‐turn components. This clearly exemplifies the hierarchical growth of the protein secondary structures, which would be important in our understanding of protein folding. While the occurrence of the O‧‧‧C═O interaction in α‐helices has been well documented, we find it to be equally important in making capping interactions at helix termini.

Intermolecular n→π* Interactions Based on a Tailored Multicarbonyl‐Containing Macrocycle

“…electrostatic dipole-dipole or n!π* orbital delocalization, [2,[5][6][7][8][9] such non-covalent interaction has recently attracted growing attentions in various disciplines. [2][3][4] Since the Raines group suggested the contribution of n!π* interaction associated with Bürgi-Dunitz trajectory to the conformational stability of collagen protein, [10,11] many efforts have dedicated to unveil the importance of n!π* interactions in proteins, [12][13][14][15][16][17][18] peptides and peptoids, [19][20][21][22] polymers, [23,24] small molecules, [25][26][27][28][29][30] and even reaction transition states. [31][32][33] On the other hand, manipulations of the intra-molecular n!π* interactions through molecular design to achieve conformational control, [34][35][36][37] engender photophysical properties, [38][39][40][41] tune supramolecular assembly, [42,43] modulate the reaction activity and selectivity [44]…”