Triple-Helix-Stabilizing Effects in Collagen Model Peptides Containing PPII-Helix-Preorganized Diproline Modules |
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| Authors: | Andreas Maaßen Dr Jan M Gebauer Elena Theres Abraham Isabelle Grimm Dr Jörg-Martin Neudörfl Dr Ronald Kühne Prof Dr Ines Neundorf Prof Dr Ulrich Baumann Prof Dr Hans-Günther Schmalz |
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| Institution: | 1. University of Cologne, Department of Chemistry, Greinstraße 4, 50939 Cologne, Germany;2. University of Cologne, Department of Chemistry, Zülpicher Straße 47a, 50674 Cologne, Germany;3. Leibniz-Institut für Molekulare Pharmakologie (FMP), Campus Berlin-Buch, Robert-Rössle-Straße 10, 13125 Berlin, Germany |
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| Abstract: | Collagen model peptides (CMPs) serve as tools for understanding stability and function of the collagen triple helix and have a potential for biomedical applications. In the past, interstrand cross-linking or conformational preconditioning of proline units through stereoelectronic effects have been utilized in the design of stabilized CMPs. To further study the effects determining collagen triple helix stability we investigated a series of CMPs containing synthetic diproline-mimicking modules (ProMs), which were preorganized in a PPII-helix-type conformation by a functionalizable intrastrand C2 bridge. Results of CD-based denaturation studies were correlated with calculated (DFT) conformational preferences of the ProM units, revealing that the relative helix stability is mainly governed by an interplay of main-chain preorganization, ring-flip preference, adaptability, and steric effects. Triple helix integrity was proven by crystal structure analysis and binding to HSP47. |
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| Keywords: | Collagen Dreifachhelix HSP47 Peptidomimetika Proteinfaltung |
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