The modification of natural collagens has proved challenging, and these difficulties are compounded by immunological problems when modified collagens are expressed in higher animals. Consequently there is a demand for collagen-like peptides (CLPs) to serve as models in which these problems are minimized.

The tertiary structure of collagen consists of a triple helix of polyproline type(II) sequences (Xaa-Yaa-Gly)_n with the consensus triplet Pro-Hyp-Gly (Hyp is (4R)-hydroxyproline). We have developed short CLPs whose assembly into collagen triple helices is directed by interchain metal-ligand interactions. The covalent attachment of 2,2'-bipyridyl ligands to the N-termini of (Pro-Hyp-Gly)₅ CLPs directs the formation of the collagen triple helix in the presence of hexacoordinate Fe²⁺. We describe the remarkable stability of these metal-assembled CLPs, and the enrichment of a preferred heterotrimeric CLP from a mixture of PPII sequences. Crystal structures of the apo-homotrimers are guiding the redesign of sequences that adopt the staggered collagen triple helix.

Figure 1. Sequences of collagen-like peptides. Chelation of Fe²⁺ by the bipyridyl groups directs trimer assembly.