| Collagen is one of the most abundant proteins found in nature, accounting for 1/4 of the dry weight of vertebrate tissue and 34 of the dry weight of human skin. By using a detailed understanding of the structure and stability of the collagen triple helix, we have developed new chemical modalities that can anchor to natural collagen. These collagen mimetic peptides are incapable of self-assembly into homotrimeric triple helices, but are able to anneal spontaneously to endogenous collagen type I. We show that such collagen mimetic peptides containing 4-fluoroproline residues, in particular, bind tightly to bovine type I collagen in vitro and to a mouse wound ex vivo. These synthetic peptides, covalently attached to fluorophores, intrinsically highlight wound regions in which endogenous collagen has suffered the most damage and requires the most urgent intervention. In addition, our collagen mimetic peptides can deliver and anchor pendant wound-healing peptides within an actual wound bed. Application of these conjugates to transgenic diabetic (db/db) mice and subsequent histological data indicate pendant-dependent expedition of wound repair. The reported results provide a proof-of-principle for using collagen mimetic peptides as an effective bio-compatible delivery system, and show promise to treat wounds differentially, based on their nature, position in the body, and cosmetic requirements. We believe that this use of synthetic peptides heralds a new era in treating wounds. |
