Triple‐Helix‐Stabilizing Effects in Collagen Model Peptides Containing PPII‐Helix‐Preorganized Diproline Modules. (3rd February 2020)

• Record Type: Journal Article
• Authors: Maaßen, Andreas; Gebauer, Jan M.; Theres Abraham, Elena; Grimm, Isabelle; Neudörfl, Jörg‐Martin; Kühne, Ronald; Neundorf, Ines; Baumann, Ulrich; Schmalz, Hans‐Günther
• Is Part Of: Angewandte Chemie. Volume 132:Number 14(2020)
• Page Start: 5796
• Page End: 5804
• Publication Date: 2020-02-03
• Subjects: Collagen -- Dreifachhelix -- HSP47 -- Peptidomimetika -- Proteinfaltung; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201914101
• Languages: English
• ISSNs: 0044-8249

Abstract

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. Abstract : Kollagenmodellpeptide sind vielversprechende Materialien für biomedizinische Anwendungen. Einblicke in die Auswirkungen von Strukturmodifikationen sind für die rationale Entwicklung von Peptideigenschaften entscheidend. Der Einfluss einer kovalenten Diprolin‐Versteifung wurde untersucht und mit theoretischen Ergebnissen korreliert, um die Zusammenwirkung (de)stabilisierender Effekte in der Tripelhelix zu verstehen.