Electrostatic versus steric effects in peptidomimicry: synthesis and secondary structure analysis of gramicidin S analogues with (E)-alkene peptide isosteres.
A concise synthetic strategy was used for the first preparation of GS analogues with trisubstituted (E)-alkene peptide bond replacements. Solution and solid state conformational analysis demonstrated that the bistrifluoromethylated analogue was a superior mimic of the natural product, whereas the incorporation of methyl groups into the alkene peptide isostere led to a far greater perturbation of the secondary structure features of GS. The difference between CF3- and CH3-substitution can be explained by the superior electrostatic carbonyl group mimicry of the former function.
Xiao
Jingbo
J
Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
Weisblum
Bernard
B
Wipf
Peter
P
D000475:Alkenes / Q000737:chemistry*; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D006096:Gramicidin / Q000031:analogs & derivatives* / Q000737:chemistry; D008958:Models, Molecular; D010456:Peptides, Cyclic / Q000737:chemistry*; D017433:Protein Structure, Secondary; D055672:Static Electricity; D013237:Stereoisomerism
D000475:Alkenes; D010456:Peptides, Cyclic; D006096:Gramicidin