Protein Design with Fluoroprolines: 4,4-Difluoroproline Does Not Eliminate the Rate-Limiting Step of Thioredoxin Folding.

ABSTRACT: C⁴ -substituted fluoroprolines (4R)-fluoroproline ((4R)-Flp) and (4S)-fluoroproline ((4S)-Flp) have been used in protein engineering to enhance the thermodynamic stability of peptides and proteins. The electron-withdrawing effect of fluorine can bias the pucker of the pyrrolidine ring, influence the conformational preference of the preceding peptide bond, and can accelerate the cis/trans prolyl peptide bond isomerisation by diminishing its double bond character. The role of 4,4-difluoroproline (Dfp) in the acceleration of the refolding rate of globular proteins bearing a proline (Pro) residue in the cis conformation in the native state remains elusive. Moreover, the impact of Dfp on the thermodynamic stability and bioactivity of globular proteins has been seldom described. In th

SUBMITTER: O' Loughlin J 

PROVIDER: S-EPMC9292674 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature