Origin of the stability conferred upon collagen by fluorination |
| |
Authors: | Matthew D. Shoulders Kimberli J. Kamer Ronald T. Raines |
| |
Affiliation: | 1. Department of Chemistry, University of Wisconsin–Madison, 1101 University Avenue, Madison, WI 53706-1322, USA;2. Department of Biomedical Engineering, University of Wisconsin–Madison, 1550 Engineering Drive, Madison, WI 53706-1609, USA;3. Department of Biochemistry, University of Wisconsin–Madison, 433 Babcock Drive, Madison, WI 53706-1544, USA |
| |
Abstract: | According to a prevailing theory, (2S,4R)-4-hydroxyproline (Hyp) residues stabilize the collagen triple helix via a stereoelectronic effect that preorganizes appropriate backbone torsion angles for triple-helix formation. This theory is consistent with the marked stability that results from replacing the hydroxyl group with the more electron-withdrawing fluoro group, as in (2S,4R)-4-fluoroproline (Flp). Nonetheless, the hyperstability of triple helices containing Flp has been attributed by others to the hydrophobic effect rather than a stereoelectronic effect. We tested this hypothesis by replacing Hyp with 4,4-difluoroproline (Dfp) in collagen-related peptides. Dfp retains the hydrophobicity of Flp, but lacks the ability of Flp to preorganize backbone torsion angles. Unlike Flp, Dfp does not endow triple helices with elevated stability, indicating that the hyperstability conferred by Flp is not due to the hydrophobic effect. |
| |
Keywords: | |
本文献已被 ScienceDirect 等数据库收录! |
|