The design, synthesis and characterization of scaffold-assembled collagen mimetics and peptide dendrimers

The collagen mimetic structures described in this dissertation are focused on the Gly-Nleu-Pro sequence. All the syntheses were carried out in solution.; Single-chain structures, Boc-(Gly-Nleu-Pro)n-OMe, can be synthesized and purified in large scale. They form triple helices when n is greater than 6. These are the building blocks for the scaffold-assembled and dendritic collagen mimetics.; We have incorporated the triserine lactone (TSL) scaffold into our collagen mimetic structures. The TSL scaffold assembles the peptide chains at the C-terminus. In both H2O and 2:1 EG/H2O, stable triple helices in solution were observed when the peptide chains reach a certain length.; A new N-terminal scaffold, TRIS, was also incorporated into our collagen mimetics. Scaffold assembly can be achieved by direct coupling between long peptide chains and the TRIS scaffold using DEPBT, a new coupling reagent developed in our group. The protecting groups at both the N- and the C-terminus of these TRIS-assembled structures can be easily removed for further modification.; Collagen mimetic dendrimers were also synthesized. The triple helical first generation dendrimer exhibits higher Tm value than the component TRIS-assembled structure. Concentration dependent thermal melting experiments revealed that the stabilizing effect arises from an intramolecular clustering of the triple helical arrays about the core structure. This cluster excludes solvent from the interior portion of the array which leads to stabilization of the triple helix bundle. Non-triple helical first and second generation dendrimers have also been prepared. The methyl esters on the periphery can be removed to attach other functional moieties for novel biomaterials.; Biotinylated single-chain collagen mimetics have been synthesized. These molecules were attached to an avidin-coated surface for bioassays. Single-chain and TRIS-assembled collagen mimetics incorporating catechol-containing moieties have also been prepared. For the single-chain molecule, when 1/3 equivalence of Fe3+ is added, the Fe3+-dopamine complex functions as an N-terminal scaffold to assemble the triple helix. For the TRIS-assembled structures with catechol-containing molecules attached at the C-terminus, addition of Fe3+ increases the T m dramatically. In these cases, Fe3+-catechol complex functions as a C-terminal scaffold which leads to triple helices with both ends of the peptide chains tethered.