TY - JOUR
T1 - Fluorinated Prolines as Conformational Tools and Reporters for Peptide and Protein Chemistry
AU - Verhoork, Sanne J.M.
AU - Killoran, Patrick M.
AU - Coxon, Christopher R.
N1 - Funding Information:
*E-mail: [email protected]. Telephone: +44 151 904 6344. ORCID Christopher R. Coxon: 0000-0002-3375-3901 Funding The authors thank Liverpool John Moores University for a generous fully funded Ph.D. scholarship for S.J.M.V. and the Engineering and Physical Sciences Council (EPSRC), UK (EP/R020299/1), for a postdoctoral fellowship for P.M.K. Notes The authors declare no competing financial interest.
Publisher Copyright:
© 2018 American Chemical Society.
PY - 2018/10/2
Y1 - 2018/10/2
N2 - Amide bonds at the proline nitrogen are particularly susceptible to rotation, affording cis and trans isomers. Installation of a stereochemically defined electron-withdrawing fluorine atom or fluorinated groups has the power to influence the cis-trans conformational preferences of the amide bond in X-(F)Pro (where X = any other amino acid). Advantageously, this also provides a sensitive reporter for 19F nuclear magnetic resonance (NMR) studies of protein conformation, interactions, and dynamics. We deliberately use the term "fluorinated prolines" as an all-encompassing term to describe proline analogues containing one or more fluorine atoms and to avoid confusion with the more well-known 4-fluoroprolines. This review presents a critical discussion of the growing repertoire of fluorinated prolines that have been described and, importantly, provides a comparison of their uses and relative influence on amide-bond conformation and discusses the significant potential of using 19F NMR as a tool to probe conformational changes in polypeptides.
AB - Amide bonds at the proline nitrogen are particularly susceptible to rotation, affording cis and trans isomers. Installation of a stereochemically defined electron-withdrawing fluorine atom or fluorinated groups has the power to influence the cis-trans conformational preferences of the amide bond in X-(F)Pro (where X = any other amino acid). Advantageously, this also provides a sensitive reporter for 19F nuclear magnetic resonance (NMR) studies of protein conformation, interactions, and dynamics. We deliberately use the term "fluorinated prolines" as an all-encompassing term to describe proline analogues containing one or more fluorine atoms and to avoid confusion with the more well-known 4-fluoroprolines. This review presents a critical discussion of the growing repertoire of fluorinated prolines that have been described and, importantly, provides a comparison of their uses and relative influence on amide-bond conformation and discusses the significant potential of using 19F NMR as a tool to probe conformational changes in polypeptides.
U2 - 10.1021/acs.biochem.8b00787
DO - 10.1021/acs.biochem.8b00787
M3 - Review article
C2 - 30277385
AN - SCOPUS:85055172328
SN - 0006-2960
VL - 57
SP - 6132
EP - 6143
JO - Biochemistry
JF - Biochemistry
IS - 43
ER -