The neurotrophic protein Nerve Growth Factor (NGF) represents a new target for the development of potential therapies for neurological disorders such as Alzheimer's disease (AD). Peptides spanning the length of the hNGF sequence were assembled using both manual and automated solid-phase procedures. These sequences were tested in a competitive assay and their ability to inhibit <SUP>125</SUP>I-GF binding to a recombinant form of the gp75 NGF-receptor assessed. Considerable levels of inihbitory activity were observed from peptides selected from the C-terminal fragment of the protein. The shortest sequence demonstrating this activity was found to span the amino acid residues Arg 100 to Arg 114. Removal of either residue from the sequence resulted in the inactivation of the peptide in the assay. This would appear to implicate both these basic side-chains in the receptor binding recognition process. Several peptides were investigated by high-field nuclear magnetic resonance spectroscopy (NMR) and a complete assignment of the spectra were made. Analysis of the through-space interactions indicated that these peptides adopt a random conformation in solution.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:649052 |
| Date | January 1992 |
| Creators | Cuthbertson, Alan S. |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1842/13537 |
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