Amino Acids

, Volume 46, Issue 10, pp 2317–2324 | Cite as

Impacts of terminal (4R)-fluoroproline and (4S)-fluoroproline residues on polyproline conformation

  • Yu-Ju Lin
  • Jia-Cherng HorngEmail author
Original Article


Many interests have been focused on prolyl cistrans isomerization which is related to protein folding and isomer-specific biochemical recognition. Since polyproline can adopt either type I (PPI) helices with all cis amide bonds or type II (PPII) helices with all trans amide bonds, it has been a valuable model to study the prolyl isomerization. Recent studies have shown that stereoelectronic effects govern the stability of PPII structure and the rate of PPII → PPI conversion. To further explore the terminal stereoelectronic effects on polyproline conformation, herein we synthesized a series of host–guest peptides in which (2S,4S)-4-fluoroproline (flp) or (2S,4R)-4-fluoroproline (Flp) residues are incorporated into the C- or N-terminal end of a peptide and studied the thermodynamic and kinetic consequences on polyproline conformation. Circular dichroism measurements revealed that inserting 4-fluoroproline residues into the C terminus of a polyproline peptide induces a great stereoelectronic effect on PPII stability and PPII → PPI conversion rates. From the C terminus, a (Flp)3 triplet stabilizes PPII structure and increases the transition barrier of PPII → PPI conversion by 1.53 kJ mol−1 while a (flp)3 triplet destabilizes PPII conformation and reduce the PPII → PPI transition barrier by 4.61 kJ mol−1. In contrast, the 4-fluoroproline substitutions at the N terminus do not exhibit distinct stereoelectronic effects on PPII stability and PPII → PPI conversion rates. Our data demonstrate that the C-terminal stereoelectronic effects have a more dramatic impact on PPII stability and PPII → PPI conversion kinetics.


Stereoelectronic effect Polyproline 4-fluoroproline Prolyl isomerization Transition state barrier 



We are grateful to Ministry of Science and Technology, Taiwan (NSC 101-2113-M-007-017-MY2 and NSC 101-2738-M-007-004) and National Tsing Hua University (102N2011E1) for support of this work. We also thank the National Center for High-performance Computing (NCHC) for computer time and facilities.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

726_2014_1783_MOESM1_ESM.pdf (2.9 mb)
Supplementary material 1 (PDF 2977 kb)


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Copyright information

© Springer-Verlag Wien 2014

Authors and Affiliations

  1. 1.Department of ChemistryNational Tsing Hua UniversityHsinchuTaiwan, ROC
  2. 2.Frontier Research Center on Fundamental and Applied Sciences of MattersNational Tsing Hua UniversityHsinchuTaiwan, ROC

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