Deoxyribosyl analogues of methionyl and isoleucyl sulfamate adenylates as inhibitors of methionyl-tRNA and isoleucyl-tRNA synthetases

Eun Kim Sung; Yeon Kim Su; Sunghoon Kim; Taehee Kang; Jeewoo Lee

doi:10.1016/j.bmcl.2005.05.035

Deoxyribosyl analogues of methionyl and isoleucyl sulfamate adenylates as inhibitors of methionyl-tRNA and isoleucyl-tRNA synthetases

Eun Kim Sung, Yeon Kim Su, Sunghoon Kim, Taehee Kang, Jeewoo Lee

Department of Pharmacy

Research output: Contribution to journal › Article › peer-review

5 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	3389-3393
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	15
Issue number	14
DOIs	https://doi.org/10.1016/j.bmcl.2005.05.035
Publication status	Published - 2005 Jul 15

Bibliographical note

Funding 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

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2005.05.035

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title = "Deoxyribosyl analogues of methionyl and isoleucyl sulfamate adenylates as inhibitors of methionyl-tRNA and isoleucyl-tRNA synthetases",

abstract = "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.",

author = "Sung, {Eun Kim} and Su, {Yeon Kim} and Sunghoon Kim and Taehee Kang and Jeewoo Lee",

note = "Funding Information: This work was supported by a grant (03-PJ2-PG4-BD02-0001) from the Ministry of Health & Welfare, Republic of Korea. ",

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doi = "10.1016/j.bmcl.2005.05.035",

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journal = "Bioorganic and Medicinal Chemistry Letters",

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T1 - Deoxyribosyl analogues of methionyl and isoleucyl sulfamate adenylates as inhibitors of methionyl-tRNA and isoleucyl-tRNA synthetases

AU - Sung, Eun Kim

AU - Su, Yeon Kim

AU - Kim, Sunghoon

AU - Kang, Taehee

AU - Lee, Jeewoo

N1 - Funding Information: This work was supported by a grant (03-PJ2-PG4-BD02-0001) from the Ministry of Health & Welfare, Republic of Korea.

PY - 2005/7/15

Y1 - 2005/7/15

N2 - 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.

AB - 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.

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Deoxyribosyl analogues of methionyl and isoleucyl sulfamate adenylates as inhibitors of methionyl-tRNA and isoleucyl-tRNA synthetases

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

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