Project Details

Description

The first objective of the proposed research is to develop an approach that allows us, for the first time ever, to study the formation and stability of helical peptide structures that are not found in nature, particularly the 4.316 and 4.616-helix. This approach is based on a conformationally rigid templating macrocycle. A rigid scaffold stabilizes the first turn of the helix by covalently fixing the first amino acid of the first and second helical turn in position. This template nucleates the helix-formation of a peptide that is connected to it. We will study the solution and solid state conformation of these templates and 4.316- and 4.616-helix-formation using CD-spectroscopy, multi-dimensional NMR techniques, and x-ray crystallography. Our results will lead to a deeper insight into helix-stabilizing and destabilizing effects and will also contribute to the elucidation of the mechanism of protein folding and to more reliable protein structure predictions. The second objective is to develop a new polymeric backbone which folds into a defined and predictable secondary structure and allows an economic synthesis. We will synthesize by solid-phase methods oligomers that are composed of an alternating sequence of m- or p-anthranilic acid and L-alpha-amino acids with high helical propensity. Using CD- spectroscopy, multidimensional NMR methods, and x-ray crystallography, we will investigate their secondary structures in solution and in the solid state. In addition, we will study the influence of amino acid side chain interactions on the structural arrangement of these oligomers. Our results will further contribute to the better understanding of biopolymer folding, in particular peptides and proteins, and allow us in the future to engineer such oligomers with helical structures into self-assembled nanotubes and molecular container compounds.
StatusFinished
Effective start/end date9/30/988/31/04

Funding

  • National Institute of General Medical Sciences: $34,733.00
  • National Institute of General Medical Sciences: $145,558.00
  • National Institute of General Medical Sciences: $126,243.00
  • National Institute of General Medical Sciences: $149,926.00

ASJC

  • Radiation
  • Spectroscopy

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