Fluoroproline flip-flop: Regiochemical reversal of a stereoelectronic effect on peptide and protein structures

Abstract

(Chemical Equation Presented) Pucker up! Structural analysis of the epimeric N-acetyl-(2R,3R)- and N-acetyl-(2R,3S)-3-fluoroproline methyl esters (1 and 2; see scheme) reveals opposing ring puckers that invert the conformational preferences of the corresponding 4-fluoroproline derivatives 3 and 4. Substitution of these fluoroprolines into proteins provides a method for controlling local conformation through stereoelectronic and steric effects. © 2006 Wiley-VCH Verlag GmbH & Co. KGaA.