STRUCTURAL INVESTIGATION OF UNNATURAL PEPTIDE HELICES

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

ASJC

  • Radiation
  • Spectroscopy

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