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Abstract Change in the neuronal nitric oxide synthase (nNOS) is a key factor in pathogenesis of a number of clinical disorders. In order to find specific molecule with ability to modify nNOS activity, the nNOS protein fragment contains the sequence around Calmadulin binding region was expressed in E. Coli. The purified recombinant protein was used as target protein and a 12-mer phage-displayed peptide library was screened to identify potential nNOS inhibitor. 10 phage clones were shown to specifically inhibit nNOS activity. DNA sequencing of the clones revealed a common amino acid sequence KPHHHPMPPQVS, we named this sequence NPI. The NPI was synthesized and showed inhibition effect on activity of freshly prepared nNOS from mice brain (inhibition rate is 25% ~ 35%). Howerever, to nNOS that lost part activity , the peptide recovered the activity in a dose-dependent fashion. Our results suggest an approach to develop new drugs to treat diseases based on nNOS disorder and understanding the process of nNOS in vivo.
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Received: 06 September 2005
Published: 25 May 2006
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