title: Optimal interstrand bridges for collagen-like biomaterials.
abstract: In some natural collagen triple helices, cysteine (Cys) residues on neighboring strands are linked by disulfide bonds, enhancing association and maintaining proper register. Similarly, Cys-Cys disulfide bridges have been used to impose specific associations between collagen-mimetic peptides (CMPs). Screening a library of disulfide linkers in silico for compatibility with collagen identifies the disulfide bridge between proximal homocysteine (Hcy) and Cys as conferring much greater stability than a Cys-Cys bridge, but only when Hcy is installed in the Xaa position of the canonical Xaa-Yaa-Gly repeat and Cys is installed in the Yaa position. Experimental evaluation of CMPs that host alternative thiols validates this design: only Hcy-Cys bridges improve triple-helical structure and stability upon disulfide-bond formation. This privileged linker can enhance CMP-based biomaterials and enable previously inaccessible molecular designs.
authors.affiliation: Department of Biochemistry and ‡Department of Chemistry, University of Wisconsin-Madison , Madison, Wisconsin 53706, United States.
authors.forename: I Caglar
authors.initials: IC
authors.lastname: Tanrikulu
authors.forename: Ronald T
authors.initials: RT
authors.lastname: Raines
mesh_terms: D003094:Collagen / Q000737:chemistry; D003545:Cysteine / Q000737:chemistry; D004220:Disulfides / Q000737:chemistry; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*
chemical_list: D004220:Disulfides; D010455:Peptides; D003094:Collagen; D003545:Cysteine