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

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

45 Citations (Scopus)

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

@article{873b3cc2c6224dc7b6634ff964bd3b63,

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",

month = aug,

day = "15",

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

language = "English",

volume = "23",

pages = "4719--4722",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier",

number = "16",

}

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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