Facile and efficient assembly of collagen-like triple helices on a TRIS scaffold

The TRIS scaffold, Boc-beta-Ala-TRIS-(OH)(3) was utilized to assemble triple helices composed of the Gly-Nleu-Pro sequence (Nleu denotes N-isobutylglycine). The scaffold assembly can be achieved efficiently through direct coupling between long peptide chains and the TRIS scaffold using DEPBT, a recently developed peptide coupling reagent. CD spectroscopy and thermal denaturation studies demonstrated that Boc-beta-Ala-TRIS-[(Gly-Nleu-Pro),-OMe](3) exhibits triple helicity in H2O when n equals 5, 6. and 8, while the shorter analogs (where n = 1 and 4) do not. TRIS-assembled structures possess several advantages over the KTA- and TREN-assembled structures previously reported from our laboratory (where KTA and TREN denotes cis-1,3,5-trimethyl cyclohexane-1,3,5-tricarboxylic acid and tris(2-aminoethyl)amine, respectively). The protecting groups on the scaffold and at the C-terminus of the TRIS-assembled peptides can be readily removed to synthesize collagen mimetic dendrimers and metal-complexing collagen-like peptides respectively, both of which can lead to further enhanced thermal stability. (c) 2007 Elsevier Inc. All rights reserved.