Synthesis and activity of analogues of the isoleucyl tRNA synthetase inhibitor SB-203207

Curtis F. Crasto; Andrew K. Forrest; Tomislav Karoli; Darren R. March; Lucy Mensah; Peter J. O'Hanlon; Michael R. Nairn; Mark D. Oldham; Weimin Yue; Martin G. Banwell; Christopher J. Easton

doi:10.1016/S0968-0896(03)00237-2

Synthesis and activity of analogues of the isoleucyl tRNA synthetase inhibitor SB-203207

Curtis F. Crasto, Andrew K. Forrest, Tomislav Karoli, Darren R. March, Lucy Mensah, Peter J. O'Hanlon, Michael R. Nairn, Mark D. Oldham, Weimin Yue, Martin G. Banwell^*, Christopher J. Easton

^*Corresponding author for this work

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

16 Citations (Scopus)

Abstract

Twenty two analogues of SB-203207 have been prepared by total synthesis, and evaluated as inhibitors of a range of tRNA synthetases. Changes to the bicyclic core, removing either the terminal amino substituent or the sulfonyl group from the side chain, and altering either the carbon skeleton or stereochemistry of the isoleucine residue, decreases the potency of inhibition of isoleucyl tRNA synthetase. Substituting the isoleucine residue with other amino acids produces inhibitors of the corresponding synthetases. In particular, a methionine derivative is 50-100 times more potent against methionyl tRNA synthetase than against any of the corresponding isoleucyl, leucyl, valyl, alanyl and prolyl synthetases.

Original language	English
Pages (from-to)	2687-2694
Number of pages	8
Journal	Bioorganic and Medicinal Chemistry
Volume	11
Issue number	13
DOIs	https://doi.org/10.1016/S0968-0896(03)00237-2
Publication status	Published - 3 Jul 2003

Access to Document

10.1016/S0968-0896(03)00237-2

Cite this

@article{fd8c81b8957248b296fa6f3498f565b4,

title = "Synthesis and activity of analogues of the isoleucyl tRNA synthetase inhibitor SB-203207",

abstract = "Twenty two analogues of SB-203207 have been prepared by total synthesis, and evaluated as inhibitors of a range of tRNA synthetases. Changes to the bicyclic core, removing either the terminal amino substituent or the sulfonyl group from the side chain, and altering either the carbon skeleton or stereochemistry of the isoleucine residue, decreases the potency of inhibition of isoleucyl tRNA synthetase. Substituting the isoleucine residue with other amino acids produces inhibitors of the corresponding synthetases. In particular, a methionine derivative is 50-100 times more potent against methionyl tRNA synthetase than against any of the corresponding isoleucyl, leucyl, valyl, alanyl and prolyl synthetases.",

author = "Crasto, {Curtis F.} and Forrest, {Andrew K.} and Tomislav Karoli and March, {Darren R.} and Lucy Mensah and O'Hanlon, {Peter J.} and Nairn, {Michael R.} and Oldham, {Mark D.} and Weimin Yue and Banwell, {Martin G.} and Easton, {Christopher J.}",

year = "2003",

month = jul,

day = "3",

doi = "10.1016/S0968-0896(03)00237-2",

language = "English",

volume = "11",

pages = "2687--2694",

journal = "Bioorganic and Medicinal Chemistry",

issn = "0968-0896",

publisher = "Elsevier Ltd.",

number = "13",

}

TY - JOUR

T1 - Synthesis and activity of analogues of the isoleucyl tRNA synthetase inhibitor SB-203207

AU - Crasto, Curtis F.

AU - Forrest, Andrew K.

AU - Karoli, Tomislav

AU - March, Darren R.

AU - Mensah, Lucy

AU - O'Hanlon, Peter J.

AU - Nairn, Michael R.

AU - Oldham, Mark D.

AU - Yue, Weimin

AU - Banwell, Martin G.

AU - Easton, Christopher J.

PY - 2003/7/3

Y1 - 2003/7/3

N2 - Twenty two analogues of SB-203207 have been prepared by total synthesis, and evaluated as inhibitors of a range of tRNA synthetases. Changes to the bicyclic core, removing either the terminal amino substituent or the sulfonyl group from the side chain, and altering either the carbon skeleton or stereochemistry of the isoleucine residue, decreases the potency of inhibition of isoleucyl tRNA synthetase. Substituting the isoleucine residue with other amino acids produces inhibitors of the corresponding synthetases. In particular, a methionine derivative is 50-100 times more potent against methionyl tRNA synthetase than against any of the corresponding isoleucyl, leucyl, valyl, alanyl and prolyl synthetases.

AB - Twenty two analogues of SB-203207 have been prepared by total synthesis, and evaluated as inhibitors of a range of tRNA synthetases. Changes to the bicyclic core, removing either the terminal amino substituent or the sulfonyl group from the side chain, and altering either the carbon skeleton or stereochemistry of the isoleucine residue, decreases the potency of inhibition of isoleucyl tRNA synthetase. Substituting the isoleucine residue with other amino acids produces inhibitors of the corresponding synthetases. In particular, a methionine derivative is 50-100 times more potent against methionyl tRNA synthetase than against any of the corresponding isoleucyl, leucyl, valyl, alanyl and prolyl synthetases.

UR - http://www.scopus.com/inward/record.url?scp=12444295104&partnerID=8YFLogxK

U2 - 10.1016/S0968-0896(03)00237-2

DO - 10.1016/S0968-0896(03)00237-2

M3 - Article

SN - 0968-0896

VL - 11

SP - 2687

EP - 2694

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

IS - 13

ER -

Synthesis and activity of analogues of the isoleucyl tRNA synthetase inhibitor SB-203207

Abstract

Access to Document

Other files and links

Fingerprint

Cite this