Peptido sulfonyl fluorides as new powerful proteasome inhibitors

Arwin J. Brouwer; Anika Jonker; Paul Werkhoven; Ethan Kuo; Nan Li; Nerea Gallastegui; Johan Kemmink; Bogdan I. Florea; Michael Groll; Herman S. Overkleeft; Rob M.J. Liskamp

doi:10.1021/jm301443r

Peptido sulfonyl fluorides as new powerful proteasome inhibitors

Arwin J. Brouwer, Anika Jonker, Paul Werkhoven, Ethan Kuo, Nan Li, Nerea Gallastegui, Johan Kemmink, Bogdan I. Florea, Michael Groll, Herman S. Overkleeft, Rob M.J. Liskamp

Chair of Biochemistry

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

66 Scopus citations

Abstract

A new class of potent proteasome inhibitors is described, of which the members contain an amino acid inspired sulfonyl fluoride as the electrophilic trap. In total, 24 peptido sulfonyl fluoride inhibitors have been designed and synthesized, which were inspired by the backbone sequences of the proteasome inhibitors bortezomib, epoxomicin, and Cbz-Leu₃-aldehyde. Nine of them were very potent proteasome inhibitors, the best of which had an IC ₅₀ of 7 nM. A number of the peptido sulfonyl fluoride inhibitors were found to be highly selective for the β5 proteasome subunit.

Original language	English
Pages (from-to)	10995-11003
Number of pages	9
Journal	Journal of Medicinal Chemistry
Volume	55
Issue number	24
DOIs	https://doi.org/10.1021/jm301443r
State	Published - 27 Dec 2012

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abstract = "A new class of potent proteasome inhibitors is described, of which the members contain an amino acid inspired sulfonyl fluoride as the electrophilic trap. In total, 24 peptido sulfonyl fluoride inhibitors have been designed and synthesized, which were inspired by the backbone sequences of the proteasome inhibitors bortezomib, epoxomicin, and Cbz-Leu3-aldehyde. Nine of them were very potent proteasome inhibitors, the best of which had an IC 50 of 7 nM. A number of the peptido sulfonyl fluoride inhibitors were found to be highly selective for the β5 proteasome subunit.",

author = "Brouwer, {Arwin J.} and Anika Jonker and Paul Werkhoven and Ethan Kuo and Nan Li and Nerea Gallastegui and Johan Kemmink and Florea, {Bogdan I.} and Michael Groll and Overkleeft, {Herman S.} and Liskamp, {Rob M.J.}",

year = "2012",

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T1 - Peptido sulfonyl fluorides as new powerful proteasome inhibitors

AU - Brouwer, Arwin J.

AU - Jonker, Anika

AU - Werkhoven, Paul

AU - Kuo, Ethan

AU - Li, Nan

AU - Gallastegui, Nerea

AU - Kemmink, Johan

AU - Florea, Bogdan I.

AU - Groll, Michael

AU - Overkleeft, Herman S.

AU - Liskamp, Rob M.J.

PY - 2012/12/27

Y1 - 2012/12/27

N2 - A new class of potent proteasome inhibitors is described, of which the members contain an amino acid inspired sulfonyl fluoride as the electrophilic trap. In total, 24 peptido sulfonyl fluoride inhibitors have been designed and synthesized, which were inspired by the backbone sequences of the proteasome inhibitors bortezomib, epoxomicin, and Cbz-Leu3-aldehyde. Nine of them were very potent proteasome inhibitors, the best of which had an IC 50 of 7 nM. A number of the peptido sulfonyl fluoride inhibitors were found to be highly selective for the β5 proteasome subunit.

AB - A new class of potent proteasome inhibitors is described, of which the members contain an amino acid inspired sulfonyl fluoride as the electrophilic trap. In total, 24 peptido sulfonyl fluoride inhibitors have been designed and synthesized, which were inspired by the backbone sequences of the proteasome inhibitors bortezomib, epoxomicin, and Cbz-Leu3-aldehyde. Nine of them were very potent proteasome inhibitors, the best of which had an IC 50 of 7 nM. A number of the peptido sulfonyl fluoride inhibitors were found to be highly selective for the β5 proteasome subunit.

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AN - SCOPUS:84871643550

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VL - 55

SP - 10995

EP - 11003

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 24

ER -

Peptido sulfonyl fluorides as new powerful proteasome inhibitors

Abstract

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