Peptide bonds, conformational effect

Kofron, J.L., Kuzmic, P., Kishore, V., Genunecker, G., Fesik, S.W. and Rich, D.H. (1992) Lithium chloride perturbation of cis-trans peptide bond equilibria effect on conformational equilibria in cyclosporin A and on time-dependent inhibition of cyclophilin. J. Am. Chem. Soc. 114 2670-2675. 

Chem. Soc., 114, 2670 (1992). Lithium Perturbation of cis-trans Peptide Bond Equilibria Effect on Conformational Equilibria in Cydosporin A and on Time-Dependent Inhibition of Cydophilin. 

From a strictly chemical point of view, the synthesis of glycosides still presents a formidable challenge to synthetic chemists in spite of major advances in the area [1], Unlike peptidic bonds, the formation of the glycosidic linkage is subject to various factors that include, among others, electronic, stereoelectronic, conformational, substituent, and reactivity effects generally associated with incipient oxocarbenium ions derived from carbohydrates. 

In this procedure the acylating molecule is the active ester formed between the amino acyl moiety and the hydroxy group of HOAt. 40 Compared to the earlier methods utilizing HOSu 41 and HOBt, 42 HOAt maintains the known ability to suppress racemization, but is much more effective in catalyzing peptide-bond formation. This efficiency of HOAt may be attributed to the possible assistance of both N2 and N7 to the amine nucleophilic attack (Scheme 2). If the preferred active ester conformation found in the crystalline state (the heterocyclic At plane lies approximately perpendicular to that of the carboxylic ester moiety)143 is preserved in solution, then assistance to nucleophilic attack on both faces of the ester is likely. 

In effect, protein structure determination is a search for the conformation of a molecule whose chemical composition is known. For this reason, conformational angles about single bonds are not constrained during refinement, and they should settle into reasonable values. Spectroscopic evidence abundantly implies that peptide bonds are planar, and some refinements constrain peptide geometry. If unconstrained, peptide bonds should settle down to within one to two degrees of planar. 

A polypeptide chain assumes the a-helical conformation because this is where H bonds can be formed most effectively. The planar conformations of peptide bonds with the =0 and -H groups trans to each other contributes to the stability of the a helix. 

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