DESIGN OF AMPHIPHILIC PEPTOID ASSEMBLIES

University Of California San Francisco, San Francisco CA

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Abstract

The inexpensive and easily synthesized heteropolymer, N- alkyglycines or peptoids have some of the characteristics that make them a reasonable manmade substitute for folded proteins. Peptoids can have many of the same physical characteristics as poly alpha-amino acids. They have tremendous side chain chemical diversity and can fold into helices that denature. However, the peptoid scaffold is not "natural", and therefore not easily degraded in the body, exhibiting a long biological half-life. These characteristics make peptoids a potential scaffold for manmade molecular function. The first step in achieving this ambitious goal is the creation of a folded peptoid structure. This research proposal follows the strategy provided by de novo alpha-helical poly peptide bundle design to construct amphiphilic peptoid helical bundles. Using a general sequence design, peptoid monomer helix propensities, a library format, and a series of high through-put initial screens, potential helical peptoid bundles will be isolated. The peptoid bundle will be characterized by CD spectroscopy, NMR spectroscopy, size exclusion chromatography, dynamic light scattering, fluorescence dye binding and sedimentation equilibrium. A stable helical bundle can be used as an architectural scaffold to present therapeutic ligands, bind ions, or catalyze transformations.