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J Med Chem. 1993 Oct 1;36(20):3005-9.

Inhibition of herpes simplex virus type 1 ribonucleotide reductase by substituted tetrapeptide derivatives.

Author information

  • 1Bio-Méga/Boehringer Ingelheim Research Inc., Laval, Québec, Canada.

Abstract

It is known that peptides corresponding to the C-terminus of the small subunit of herpes simplex virus type 1 and 2 ribonucleotide reductase can inhibit enzymatic activity by preventing the association of the enzyme's two subunits. In a quest for smaller, more potent inhibitors, we have conducted a structure activity investigation based on the pentapeptide H-Val-Val-Asn-Asp-Leu-OH. Potency increases of up to 4000 times (IC50 0.18 microM) have been achieved in an enzymatic assay by a combination of modifying the N-terminal valine to a diethylacetyl group, adding a methyl group to the beta-carbon of the adjacent valine, dialkylating the asparagine side-chain nitrogen and dimethylating the beta-carbon of the aspartic acid residue. In addition the relative contribution of various inhibitor functionalities to inhibitor potency has been investigated.

PMID:
8411018
[PubMed - indexed for MEDLINE]
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