Using Structural Information of Peptides, Derived from NMR Spectroscopy, in Pharmaceutical Chemistry
Keywords:Chemical sensors, G-protein coupled receptors, Neuropeptide y, Nmr, Pharmaceutical chemistry
AbstractThe significance of information gained from the solution structure of peptides for pharmaceutical research is demonstrated with two examples: the neuropeptide Y (NPY) hormone system and a undecapeptide designed for use as a chemical sensor. In the case of NPY, the structure of the homodimer and the mode of membrane association was determined. Thereby, it was discovered that the membrane/NPY interface is formed by the same hydrophobic residues that constitute the homodimer interface. Furthermore, in the membrane-bound state, the C-terminal helix is stabilized, which is of special functional importance for the C-terminal tetrapeptide. Receptor-subtype specificity of NPY mutants may be explained through pre-orientation of residues relative to the different membrane compartments. In the case of the undecapeptide designed for use in a chemical sensor, structural information from NMR helped us to design and optimize a peptide whose unligated form is unstructured in solution but adopts a unique helical fold upon addition of sulfate. The sulfate binding pocket is formed by the N-terminal first turn.
How to Cite
R. Bader, M. Lerch, G. Folkers, O. Zerbe, Chimia 2000, 54, 627, DOI: 10.2533/chimia.2000.627.
Copyright (c) 2000 Swiss Chemical Society
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