Optimal interstrand bridges for collagen-like biomaterials

J Am Chem Soc. 2014 Oct 1;136(39):13490-3. doi: 10.1021/ja505426g. Epub 2014 Sep 23.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Collagen / chemistry
  • Cysteine / chemistry
  • Disulfides / chemistry
  • Models, Molecular
  • Peptides / chemistry*


  • Disulfides
  • Peptides
  • Collagen
  • Cysteine