Multivalent peptide dendrimers for targeting

PMSE 432

Brett A. Helms, b.helms@tue.nl1, Ingrid van Baal, i.v.baal@tue.nl1, Peggy T. H. M. de Graaf-Heuvelmans, P.T.H.M.d.Graaf@tue.nl2, Maarten Merkx, m.merkx@tue.nl2, and E. W. Meijer, E.W.Meijer@tue.nl1. (1) Laboratory of Macromolecular and Organic Chemistry, Eindhoven University of Technology, P.O. Box 513, Eindhoven, 5600 MB, Netherlands, (2) Department of Biomedical Engineering, Eindhoven University of Technology, P.O. Box 513, Eindhoven, 5600 MB, Netherlands
We will describe our most recent research towards functional biomaterials for targeting and molecular imaging. Our molecular design is based on concepts drawn from phage display, a technique in molecular biology used to identify peptide sequences that bind in a specific manner with high affinity towards a substrate of interest. Our phage mimics are derived dendritic polymers. These materials are functionalized with multiple copies (n = 2-5) of targeting peptides identified from phage display using native chemical ligation. Our synthetic methodology further allows for the incorporation of fluorescent dyes and other labels in addition to the multivalent targeting scheme. These bioconjugates are ideally suited to the investigation of multivalent ligand-receptor interactions. The design concepts presented here will be placed in a larger context of how multivalent, dynamic, noncovalent interactions may be harnessed in biomaterials such as ours for more effective molecular medicines in the identification and treatment of disease.