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The small molecule tool (S)-(-)-blebbistatin

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The small molecule tool (S)-(-)-blebbistatin : novel insights of relevance to myosin inhibitor design. / Lucas-Lopez, Cristina; Allingham, John S.; Lebl, Tomas; Lawson, Christopher P. A. T.; Brenk, Ruth; Sellers, James R.; Rayment, Ivan; Westwood, Nicholas J.

In: Organic and Biomolecular Chemistry, Vol. 6, No. 12, 2008, p. 2076-2084.

Research output: Contribution to journalArticle

Harvard

Lucas-Lopez, C, Allingham, JS, Lebl, T, Lawson, CPAT, Brenk, R, Sellers, JR, Rayment, I & Westwood, NJ 2008, 'The small molecule tool (S)-(-)-blebbistatin: novel insights of relevance to myosin inhibitor design' Organic and Biomolecular Chemistry, vol 6, no. 12, pp. 2076-2084., 10.1039/b801223g

APA

Lucas-Lopez, C., Allingham, J. S., Lebl, T., Lawson, C. P. A. T., Brenk, R., Sellers, J. R., ... Westwood, N. J. (2008). The small molecule tool (S)-(-)-blebbistatin: novel insights of relevance to myosin inhibitor design. Organic and Biomolecular Chemistry, 6(12), 2076-2084. 10.1039/b801223g

Vancouver

Lucas-Lopez C, Allingham JS, Lebl T, Lawson CPAT, Brenk R, Sellers JR et al. The small molecule tool (S)-(-)-blebbistatin: novel insights of relevance to myosin inhibitor design. Organic and Biomolecular Chemistry. 2008;6(12):2076-2084. Available from: 10.1039/b801223g

Author

Lucas-Lopez, Cristina; Allingham, John S.; Lebl, Tomas; Lawson, Christopher P. A. T.; Brenk, Ruth; Sellers, James R.; Rayment, Ivan; Westwood, Nicholas J. / The small molecule tool (S)-(-)-blebbistatin : novel insights of relevance to myosin inhibitor design.

In: Organic and Biomolecular Chemistry, Vol. 6, No. 12, 2008, p. 2076-2084.

Research output: Contribution to journalArticle

Bibtex - Download

@article{1b2133ce43024f7dacab09721e93297b,
title = "The small molecule tool (S)-(-)-blebbistatin: novel insights of relevance to myosin inhibitor design",
keywords = "BLEBBISTATIN INHIBITION, MOTOR DOMAIN, CONTRACTILE RING, II INHIBITOR, CYTOKINESIS, MECHANISM, CELLS, SPECIFICITY, KINASE, ACTIN",
author = "Cristina Lucas-Lopez and Allingham, {John S.} and Tomas Lebl and Lawson, {Christopher P. A. T.} and Ruth Brenk and Sellers, {James R.} and Ivan Rayment and Westwood, {Nicholas J.}",
year = "2008",
doi = "10.1039/b801223g",
volume = "6",
number = "12",
pages = "2076--2084",
journal = "Organic and Biomolecular Chemistry",
issn = "1477-0520",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - The small molecule tool (S)-(-)-blebbistatin

T2 - novel insights of relevance to myosin inhibitor design

A1 - Lucas-Lopez,Cristina

A1 - Allingham,John S.

A1 - Lebl,Tomas

A1 - Lawson,Christopher P. A. T.

A1 - Brenk,Ruth

A1 - Sellers,James R.

A1 - Rayment,Ivan

A1 - Westwood,Nicholas J.

AU - Lucas-Lopez,Cristina

AU - Allingham,John S.

AU - Lebl,Tomas

AU - Lawson,Christopher P. A. T.

AU - Brenk,Ruth

AU - Sellers,James R.

AU - Rayment,Ivan

AU - Westwood,Nicholas J.

PY - 2008

Y1 - 2008

N2 - <p>The small molecule blebbistatin is now a front line tool in the study of myosin function. Chemical modi. cation of the tricyclic core of blebbistatin could deliver the next generation of myosin inhibitors and to help address this we report here on the impact of structural changes in the methyl-substituted aromatic ring of blebbistatin on its biological activity. Chemical methods for the preparation of isomeric methyl-containing analogues are reported and a series of co-crystal structures are used to rationalise the observed variations in their biological activity. These studies further support the view that the previously identified binding mode of blebbistatin to Dictyostelium discoideum myosin II is of relevance to its mode of action. A discussion of the role that these observations have on planning the synthesis of focused libraries of blebbistatin analogues is also provided including an assessment of possibilities by computational methods. These studies are ultimately directed at the development of novel myosin inhibitors with improved affinity and different selectivity profiles from blebbistatin itself.</p>

AB - <p>The small molecule blebbistatin is now a front line tool in the study of myosin function. Chemical modi. cation of the tricyclic core of blebbistatin could deliver the next generation of myosin inhibitors and to help address this we report here on the impact of structural changes in the methyl-substituted aromatic ring of blebbistatin on its biological activity. Chemical methods for the preparation of isomeric methyl-containing analogues are reported and a series of co-crystal structures are used to rationalise the observed variations in their biological activity. These studies further support the view that the previously identified binding mode of blebbistatin to Dictyostelium discoideum myosin II is of relevance to its mode of action. A discussion of the role that these observations have on planning the synthesis of focused libraries of blebbistatin analogues is also provided including an assessment of possibilities by computational methods. These studies are ultimately directed at the development of novel myosin inhibitors with improved affinity and different selectivity profiles from blebbistatin itself.</p>

KW - BLEBBISTATIN INHIBITION

KW - MOTOR DOMAIN

KW - CONTRACTILE RING

KW - II INHIBITOR

KW - CYTOKINESIS

KW - MECHANISM

KW - CELLS

KW - SPECIFICITY

KW - KINASE

KW - ACTIN

U2 - 10.1039/b801223g

DO - 10.1039/b801223g

M1 - Article

JO - Organic and Biomolecular Chemistry

JF - Organic and Biomolecular Chemistry

SN - 1477-0520

IS - 12

VL - 6

SP - 2076

EP - 2084

ER -

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