Peptide functionalised discotic amphiphiles and their self-assembly into supramolecular nanofibres
作者:P. Besenius、Y. Goedegebure、M. Driesse、M. Koay、P. H. H. Bomans、A. R. A. Palmans、P. Y. W. Dankers、E. W. Meijer
DOI:10.1039/c1sm05896g
日期:——
The multicomponent co-assembly of discotic amphiphiles provides a modular and versatile approach to prepare RGDS- and PHSRN-peptide functionalised supramolecular nanofibres, bearing pendant paramagnetic Gd(III)-chelates.
Supramolecular polymers have shown to be powerful scaffolds for tissue engineering applications. Supramolecular biomaterials functionalized with ureidopyrimidinone (UPy) moieties, which dimerize via quadruple hydrogen-bond formation, are eminently suitable for this purpose. The conjugation of the UPy moiety to biologically active peptides ensures adequate integration into the supramolecular UPy polymer matrix. The structural complexity of UPy-peptide conjugates makes their synthesis challenging and until recently low yielding, thus restricted the access to structurally diverse derivatives. Here we report optimization studies of a convergent solid-phase based synthesis of UPy-modified peptides. The peptide moiety is synthesized using standard Fmoc solid-phase synthesis and the UPy fragment is introduced on the solid-phase simplifying the synthesis and purification of the final UPy-peptide conjugate. The convergent nature of the synthesis reduces the number of synthetic steps in the longest linear sequence compared to other synthetic approaches. We demonstrate the utility of the optimized route by synthesizing a diverse range of biologically active UPy-peptide bioconjugates in multimilligram scale for diverse biomaterial applications. 1 Introduction 2 Divergent Synthesis 3 Convergent Synthesis 4 UPy-Amine Strategy 5 UPy-Carboxylic Acid Strategy 6 Conclusion