STUDIES ON BETA-AMINOACID OLIGOMERS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our group is involved in the design and study of unnatural polymeric systems, principally beta-amino acid oligomers. These molecules are of interest because they mimic natural peptides and proteins in that they have well defined folding patterns. The actual structures that they form as well as the stability of these folded forms differ dramatically from natural systems. Unnatural peptide systems have potential uses as drugs (we are presently investigating polycationic beta-amino acid antimicrobial agents) as well as structural scaffolds for catalyst design and other polymer aplications. Structural information about these oligomers is necessary for their rational design and the interprestation of their biological properties. Previous work in our group has made good use of high field NMR to elucidate the structure of several beta-amino acid oligomers (J. Am. Chem. Soc. 2000, 122, 4821-4822 ). That study investigated the structural effects of making substitutions of cyclopentyl based beta-amino acid residues by pyrolidine based residues. The present study is investigating the effects of acyclic residues on oligomer structure. As with the previous work on similar systems, structure elucidation in non-aqueous solution (CD3OH) has proved to be straight forward due to good dispersion and observation of strong long range ROEs of 500 and 600 MHz spectrometers. Structural studies in aqueous solution are complicated by poor dispersion and weaker long range ROEs. This is a consequence of there being less structure in aqueous solution. We believe, as was the case in similar molecules, that the enhanced sensitivity of the 750MHz NMR will aid in the resolution of signals and in the detection of more long-range ROEs.