| Project/Area Number |
16390016
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Physical pharmacy
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| Research Institution | Osaka University of Pharmaceutical Sciences (2005)
Osaka University (2004) |
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Principal Investigator |
KOBAYASHI Yuji Osaka University of Pharmaceutical Sciences, Department of Pharmaceutical Sciences, Visiting Professor, 薬学部, 客員教授 (20127228)
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| Co-Investigator(Kenkyū-buntansha) |
OHKUBO Tadayasu Osaka University, Graduate School of Pharmaceutical Sciences, Associate Professor, 大学院・薬学研究科, 助教授 (90272997)
YOSHIDA Takuya Osaka University, Graduate School of Pharmaceutical Sciences, Research Associate, 大学院・薬学研究科, 助手 (00294116)
NISHI Yoshinori Osaka University of Pharmaceutical Sciences, Visiting Scientist, 薬学研究科, 客員研究員 (70397727)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥9,500,000 (Direct Cost: ¥9,500,000)
Fiscal Year 2005: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2004: ¥6,600,000 (Direct Cost: ¥6,600,000)
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| Keywords | collagen model peptides / triple helical structure / 4-hydroxyproline / 4-fluoroproline / enthalpy / entropy / partial molar volume / hydration / ヒドロキシプロリン / フルオロプロリン / コラーゲンモデルペブチド / トリプルヘリックス |
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| Research Abstract |
It has been known that Hyp^R residue contributes to the thermal stability of the collagen triple helical structure. We have performed intensive studies to investigate the stabilizing mechanism of the collagen triple helical structure using a series of polytripeptides (X-Y-Gly)_n [X, Y : Pro, Hyp^R, or 4-fluoroproline (fPro)] from the thermodynamic point of view. The thermodynamic parameters with the transition from the triple-helix to the single-coil determined by DSC analyses indicated that the enhanced stabilities are classified into two different types : the enthalpy term is primarily responsible for increased stability of (Pro-Hyp^R-Gly)_<10>, whereas the entropy term dominates the enhanced stabilities of (Pro-fPro^R-Gly)_<10> and (fPro^s-Pro-Gly)_<10>. We showed that this difference comes from the difference of hydration on these peptides by the comparison of molecular volumes observed in solution with intrinsic ones from the crystal structure.
On the other hand, it has been shown
… More
that Hyp^R residue at the X position decreases the stability of the triple helix. To address this effect of Hyp^R, we have synthesized and characterized (Hyp^R-Hyp^R-Gly)_<10>. We have already reported that it takes a thermally stable triple helix, however, its stabilizing mechanism has not been solved. Here we determined the full-length crystal structure of (Hyp^R-Hyp^R-Gly)_<10>. To corroborate this precise structural information, we estimated the degrees of hydration in both the triple-helix and the single-coil states. The results showed that the degree of hydration of (Hyp^R-Hyp^R-Gly)_<10> is comparable to that of (Pro-Hyp^R-Gly)_<10> in the triple-helix state, but the former was more highly hydrated than (Pro-Hyp^R-Gly)_<10> in the single-coil state. Because hydration reduces the enthalpy due to the formation of hydrogen bond with water molecule and diminishes the entropy due to the restriction of water molecules surrounding a peptide molecule, we deduced that the high thermal stability of (Hyp^R-Hyp^R-Gly)_<10> is attributed to its high degree of hydration in the single-coil state. Less
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