Exploring the potential of 3'-O-carboxy esters of thymidine as inhibitors of ribonuclease A and angiogenin.

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Ghosh KS, Debnath J, Dutta P, Sahoo BK, Dasgupta S

Exploring the potential of 3'-O-carboxy esters of thymidine as inhibitors of ribonuclease A and angiogenin.

Bioorg Med Chem. 2008 Mar 15;16(6):2819-28. doi: 10.1016/j.bmc.2008.01.003. Epub 2008 Jan 10.

PubMed ID

18226913 [ View in PubMed

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Abstract

In this study, compounds with a carboxy ester in lieu of the phosphate ester at the 3'-position have been employed to inhibit the ribonucleolytic activity of ribonuclease A (RNase A). Phosphates at the 3'-position of pyrimidine bases are well-known inhibitors of the protein. We have investigated the inhibition of RNase A by 3'-O-carboxy esters of thymidine. The compounds behave as competitive inhibitors with inhibition constants ranging from 42 to 95 microM. The mode of inhibition has also been confirmed by (1)H NMR studies of the active site histidines of RNase A. Docking studies have further substantiated the experimental results. The compounds are also found to inhibit the ribonucleolytic activity of angiogenin, a homologous protein and potent inducer of blood vessel formation.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Cytidine 3'-monophosphate	Ribonuclease pancreatic	IC 50 (nM)	312000	N/A	N/A	Details
Cytidine 3'-monophosphate	Ribonuclease pancreatic	Ki (nM)	103000	N/A	N/A	Details