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

Institute of Pharmaceutical Science

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

44 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
Number of pages	4
Journal	BIOORGANIC AND MEDICINAL CHEMISTRY LETTERS
Volume	23
Issue number	16
Early online date	29 May 2013
DOIs	https://doi.org/10.1016/j.bmcl.2013.05.066
Publication status	Published - 15 Aug 2013

Keywords

Cancer,
Mass spectrometry
Protein:protein interaction inhibitor
STAT3

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bmcl.2013.05.066

http://www.sciencedirect.com/science/article/pii/S0960894X13006616

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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.",

keywords = "Cancer, , Mass spectrometry, Protein:protein interaction inhibitor, STAT3",

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}",

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language = "English",

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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.

KW - Cancer,

KW - Mass spectrometry

KW - Protein:protein interaction inhibitor

KW - STAT3

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

Keywords

UN SDGs

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