Browsing by Author "Bhatt, Megh R."
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Item Proline C–H bonds as loci for proline assembly via C–H/O interactions(ChemBioChem, 2022-09-21) Daniecki, Noah J.; Bhatt, Megh R.; Yap, Glenn P. A.; Zondlo, Neal JosephProline residues within proteins lack a traditional hydrogen bond donor. However, the hydrogens of proline are all sterically accessible, with polarized C–H bonds that can be sites for molecular recognition. C–H/O interactions, between proline C–H bonds and oxygen lone pairs, have been previously identified as modes of recognition in proteins. A series of proline derivatives was synthesized, including 4R-hydroxyproline nitrobenzoate methyl ester, acylated on the proline nitrogen with bromoacetyl and glycolyl groups, and Boc-4S-(4-iodophenyl)hydroxyproline methyl amide. All three derivatives exhibited multiple close intermolecular C–H/O interactions in the crystallographic state, with H•••O distances as close as 2.3 Å. These observed distances are well below the 2.72 Å sum of the van der Waals radii of H and O. We further analyzed the role of C–H/O interactions in all previously crystallized derivatives of these amino acids, and found that all 26 structures exhibited close intermolecular C–H/O interactions. Finally, we analyzed all proline residues in the Cambridge Structural Database. The majority of these structures exhibited intermolecular C–H/O interactions at proline C–H bonds, suggesting that C–H/O interactions are an inherent and important mode for recognition of and higher-order assembly at proline residues. Due to steric accessibility and multiple polarized C–H bonds, proline residues are uniquely positioned as sites for binding and recognition via C–H/O interactions.