Stereoelectronic effects on collagen stability: the dichotomy of 4-fluoroproline diastereomers.
Collagen is the most abundant protein in animals. Natural collagen consists of a triple helix of (Xaa-Yaa-Gly)n chains, in which the Xaa and Yaa residues are often l-proline. Here, a (2S,4S)-4-fluoroproline (flp) residue is shown to be greatly stabilizing in the Xaa position (but destabilizing in the Yaa position). In contrast, a (2S,4R)-4-fluoroproline (Flp) residue is shown to be greatly destabilizing in the Xaa position (but stabilizing in the Yaa position). The dichotomous effect of the diastereomers appears to arise from a gauche effect, which alters pyrrolidine ring pucker and hence properly (or improperly) preorganizes main-chain dihedral angles. Thus, the rational use of stereoelectronic effects can enhance the conformational stability of a protein.
Hodges
Jonathan A
JA
Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53706, USA.
Raines
Ronald T
RT
D002942:Circular Dichroism; D003094:Collagen / Q000737:chemistry*; D006909:Hydroxyproline / Q000737:chemistry; D011392:Proline / Q000031:analogs & derivatives / Q000737:chemistry*; D017510:Protein Folding; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
C431803:fluoro-proline; D003094:Collagen; D011392:Proline; D006909:Hydroxyproline