Investigation of the protein alkylation sites of the STAT3:STAT3 inhibitor Stattic by mass spectrometry

Sibylle Heidelberger; Giovanna Zinzalla; Dyeison Antonow; Samantha Essex; B. Piku Basu; Jonathan Palmer; Jarmila Husby; Paul J. M. Jackson; Khondaker M. Rahman; Andrew F. Wilderspin; Mire Zloh; David E. Thurston

doi:10.1016/j.bmcl.2013.05.066

Investigation of the protein alkylation sites of the STAT3:STAT3 inhibitor Stattic by mass spectrometry

Sibylle Heidelberger, Giovanna Zinzalla, Dyeison Antonow, Samantha Essex, B. Piku Basu, Jonathan Palmer, Jarmila Husby, Paul J. M. Jackson, Khondaker M. Rahman, Andrew F. Wilderspin, Mire Zloh, David E. Thurston

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Abstract

STAT3 (Signal Transducer and Activator of Transcription factor 3) is constitutively active in a wide range of human tumours. Stattic is one of the first non-peptidic small molecules reported to inhibit formation of the STAT3:STAT3 protein dimer complex. A mass spectrometry method has been developed to investigate the binding of Stattic to the un-phosphorylated STAT3βtc (U-STAT3) protein. Alkylation of four cysteine residues has been observed with possible reaction at a fifth which could account for the mechanism of action.

Original language	English
Pages (from-to)	4719-4722
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	23
Issue number	16
DOIs	https://doi.org/10.1016/j.bmcl.2013.05.066
Publication status	Published - 15 Aug 2013

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10.1016/j.bmcl.2013.05.066

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Heidelberger, S., Zinzalla, G., Antonow, D., Essex, S., Piku Basu, B., Palmer, J., Husby, J., Jackson, P. J. M., Rahman, K. M., Wilderspin, A. F., Zloh, M., & Thurston, D. E. (2013). Investigation of the protein alkylation sites of the STAT3:STAT3 inhibitor Stattic by mass spectrometry. Bioorganic and Medicinal Chemistry Letters, 23(16), 4719-4722. https://doi.org/10.1016/j.bmcl.2013.05.066

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title = "Investigation of the protein alkylation sites of the STAT3:STAT3 inhibitor Stattic by mass spectrometry",

abstract = "STAT3 (Signal Transducer and Activator of Transcription factor 3) is constitutively active in a wide range of human tumours. Stattic is one of the first non-peptidic small molecules reported to inhibit formation of the STAT3:STAT3 protein dimer complex. A mass spectrometry method has been developed to investigate the binding of Stattic to the un-phosphorylated STAT3βtc (U-STAT3) protein. Alkylation of four cysteine residues has been observed with possible reaction at a fifth which could account for the mechanism of action.",

author = "Sibylle Heidelberger and Giovanna Zinzalla and Dyeison Antonow and Samantha Essex and {Piku Basu}, B. and Jonathan Palmer and Jarmila Husby and Jackson, {Paul J. M.} and Rahman, {Khondaker M.} and Wilderspin, {Andrew F.} and Mire Zloh and Thurston, {David E.}",

year = "2013",

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doi = "10.1016/j.bmcl.2013.05.066",

language = "English",

volume = "23",

pages = "4719--4722",

journal = "Bioorganic and Medicinal Chemistry Letters",

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publisher = "Elsevier",

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Heidelberger, S, Zinzalla, G, Antonow, D, Essex, S, Piku Basu, B, Palmer, J, Husby, J, Jackson, PJM, Rahman, KM, Wilderspin, AF, Zloh, M & Thurston, DE 2013, 'Investigation of the protein alkylation sites of the STAT3:STAT3 inhibitor Stattic by mass spectrometry', Bioorganic and Medicinal Chemistry Letters, vol. 23, no. 16, pp. 4719-4722. https://doi.org/10.1016/j.bmcl.2013.05.066

TY - JOUR

T1 - Investigation of the protein alkylation sites of the STAT3:STAT3 inhibitor Stattic by mass spectrometry

AU - Heidelberger, Sibylle

AU - Zinzalla, Giovanna

AU - Antonow, Dyeison

AU - Essex, Samantha

AU - Piku Basu, B.

AU - Palmer, Jonathan

AU - Husby, Jarmila

AU - Jackson, Paul J. M.

AU - Rahman, Khondaker M.

AU - Wilderspin, Andrew F.

AU - Zloh, Mire

AU - Thurston, David E.

PY - 2013/8/15

Y1 - 2013/8/15

N2 - STAT3 (Signal Transducer and Activator of Transcription factor 3) is constitutively active in a wide range of human tumours. Stattic is one of the first non-peptidic small molecules reported to inhibit formation of the STAT3:STAT3 protein dimer complex. A mass spectrometry method has been developed to investigate the binding of Stattic to the un-phosphorylated STAT3βtc (U-STAT3) protein. Alkylation of four cysteine residues has been observed with possible reaction at a fifth which could account for the mechanism of action.

AB - STAT3 (Signal Transducer and Activator of Transcription factor 3) is constitutively active in a wide range of human tumours. Stattic is one of the first non-peptidic small molecules reported to inhibit formation of the STAT3:STAT3 protein dimer complex. A mass spectrometry method has been developed to investigate the binding of Stattic to the un-phosphorylated STAT3βtc (U-STAT3) protein. Alkylation of four cysteine residues has been observed with possible reaction at a fifth which could account for the mechanism of action.

U2 - 10.1016/j.bmcl.2013.05.066

DO - 10.1016/j.bmcl.2013.05.066

M3 - Article

C2 - 23810499

SN - 0960-894X

VL - 23

SP - 4719

EP - 4722

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 16

ER -

Investigation of the protein alkylation sites of the STAT3:STAT3 inhibitor Stattic by mass spectrometry

Abstract

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