2′-Deoxy, 3′-deoxy, and 2′,3′-dideoxyribosyl surrogates of isoleucyl and methionyl sulfamate adenylates have been investigated to identify the pharmacophoric importance of the ribose group for the inhibition of Escherichia coli methionyl-tRNA (MRS) and isoleucyl-tRNA (IRS) synthetases. Molecular modeling of 2′,3′-dideoxyribosyl Met-NHSO2-AMP (9) with the crystal structure of E. coli MRS revealed that the lack of the two hydroxyl groups on ribose was compensated by the formation of an extra hydrogen bond between the ring oxygen and His24, resulting in a small activity reduction.
Bibliographical noteFunding Information:
This work was supported by a grant (03-PJ2-PG4-BD02-0001) from the Ministry of Health & Welfare, Republic of Korea.
All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry