title: Impacts of terminal (4R)-fluoroproline and (4S)-fluoroproline residues on polyproline conformation.
abstract: Many interests have been focused on prolyl cis-trans 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.
authors.affiliation: Department of Chemistry, National Tsing Hua University, Hsinchu, 30013, Taiwan, ROC.
authors.forename: Yu-Ju
authors.initials: YJ
authors.lastname: Lin
authors.forename: Jia-Cherng
authors.initials: JC
authors.lastname: Horng
mesh_terms: D000595:Amino Acid Sequence; D002942:Circular Dichroism; D005461:Fluorine / Q000737:chemistry; D054879:Halogenation; D007700:Kinetics; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D011392:Proline / Q000031:analogs & derivatives* / Q000737:chemistry; D011487:Protein Conformation; D017510:Protein Folding; D055550:Protein Stability; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013237:Stereoisomerism; D013816:Thermodynamics
chemical_list: D009842:Oligopeptides; D010455:Peptides; C431803:fluoro-proline; C011083:polyproline; D005461:Fluorine; D011392:Proline