Metal-Ligand Interactions to Promote the Assembly of a Collagen Peptide into Fibrils

摘要

Collagen is one of the most abundant proteins that accounts for approximately one third of the total protein content within humans [1]. The primary structure of collagen is composed of a trimeric repeating unit, most commonly Xaa-Yaa-Gly, where Xaa and Yaa are most often L-proline and 4(R)-hydroxy-L-proline [2]. This sequence forms a left-handed polyproline type II (PPII) helical conformation. Three strands of the PPII helix assemble and form the overall right-handed triple helical structure of collagen. This rigid structure serves many functions throughout the body, such as in tendons, ligaments, bones, and the extracellular matrix. Because of the versatility of collagen, many researchers have sought ways to mimic natural collagen. Such mimics could play a crucial role in regenerative medicine in addition to offering novel biomaterials. To date, a number of research groups have investigated new collagen materials using short collagen mimetic peptides (CMPs) [3]. One such method for triggering CMP assembly is to incorporate ligands for metal ions within the sequence [4]. Metal-ligand interactions between triple helices promote the assembly of larger collagen based structures. Our designed system (Figure 1) was modeled after the metal-ligand interactions found within a variety of bacterial siderophores that contain a catechol moiety. Siderophores have an exquisite ability to chelate iron (III) [5]. With this knowledge, we aimed to promote the radial assembly of the CMP into a collagen mimetic. We designed a CMP with repeating units of Pro-Hyp-Gly, with the catechols attached via lysine side chains to have the attachment of the catechol moieties positioned along the backbone of the peptide thus allowing the ligands to extend from the collagen triple helix. We hypothesized that addition of Fe~(3+) ions would elicit a radial assembly through the interaction of the catechol moieties between neighboring collagen triple helices.