title: Different effects of 4-hydroxyproline and 4-fluoroproline on the stability of collagen triple helix.
abstract: Differential scanning calorimetry (DSC) analyses of a series of collagen model peptides suggest that 4-hydroxyproline (Hyp) and 4-fluoroproline (fPro) have different effects on the stability of the collagen triple helices according to the sequence of amino acids and stereochemistry at the 4 positions of these imino acids. The thermodynamic parameters indicate that the enhanced stabilities are classified into two different types: the enthalpy term is primarily responsible for the enhanced stability of the triple helix of (Pro-Hyp(R)-Gly)(10), whereas the entropy term dominates the enhanced stability of (Pro-fPro(R)-Gly)(10). The difference between the molecular volumes observed in solution and intrinsic molecular volumes calculated from the crystal structure indicates the different hydration states of these peptides. (Pro-Hyp(R)-Gly)(10) is highly hydrated compared to (Pro-Pro-Gly)(10), which contributes to the larger enthalpy. In contrast, the volume of (Pro-fPro(R)-Gly)(10) shows a smaller degree of hydration than that of (Pro-Pro-Gly)(10). The entropic cost of forming the triple helix of the fPro-containing peptides is compensated by a decrease in an ordered structure of water molecules surrounding the peptide molecule, although the contribution of enthalpy originating from the hydration is reduced. These arguments about the different contribution of entropic and enthalpic terms were successfully applied to interpret the stability of the triple helix of (fPro(S)-Pro-Gly)(10) as well.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Nishi
authors.forename: Susumu
authors.initials: S
authors.lastname: Uchiyama
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Doi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nishiuchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakazawa
authors.forename: Tadayasu
authors.initials: T
authors.lastname: Ohkubo
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kobayashi
mesh_terms: D000595:Amino Acid Sequence; D002152:Calorimetry, Differential Scanning; D002942:Circular Dichroism; D003094:Collagen / Q000737:chemistry*; D004355:Drug Stability; D006909:Hydroxyproline / Q000737:chemistry*; D066298:In Vitro Techniques; D008970:Molecular Weight; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry; D011392:Proline / Q000031:analogs & derivatives* / Q000737:chemistry*; D017433:Protein Structure, Secondary; D013816:Thermodynamics
chemical_list: D010455:Peptides; C431803:fluoro-proline; D003094:Collagen; D011392:Proline; D006909:Hydroxyproline