A Linker for the Solid-Phase Synthesis of Hydroxamic Acids and Identification of HDAC6 Inhibitors

Claus Gunnar Bang; Jakob Feldthusen Jensen; Anders Emil O'Hanlon Cohrt; Lasse Bohn Olsen; Saba Gebremedhin Siyum; Kim Thollund Mortensen; Tine Skovgaard; Jens Berthelsen; Liang Yang; Michael Givskov; Katrine Qvortrup; Thomas Eiland Nielsen

doi:10.1021/acscombsci.7b00068

A Linker for the Solid-Phase Synthesis of Hydroxamic Acids and Identification of HDAC6 Inhibitors

Claus Gunnar Bang, Jakob Feldthusen Jensen, Anders Emil O'Hanlon Cohrt, Lasse Bohn Olsen, Saba Gebremedhin Siyum, Kim Thollund Mortensen, Tine Skovgaard, Jens Berthelsen, Liang Yang, Michael Givskov, Katrine Qvortrup, Thomas Eiland Nielsen

Department of Chemistry

Research output: Contribution to journal › Journal article › Research › peer-review

Abstract

We herein present broadly useful, readily available and nonintegral hydroxylamine linkers for the routine solid-phase synthesis of hydroxamic acids. The developed protocols enable the efficient synthesis and release of a wide range of hydroxamic acids from various resins, relying on high control and flexibility with respect to reagents and synthetic processes. A trityl-based hydroxylamine linker was used to synthesize a library of peptide hydroxamic acids. The inhibitory effects of the compounds were examined for seven HDAC enzyme subtypes using a chemiluminescence-based assay.

Original language	English
Journal	A C S Combinatorial Science
Volume	19
Issue number	10
Pages (from-to)	657-669
ISSN	2156-8952
DOIs	https://doi.org/10.1021/acscombsci.7b00068
Publication status	Published - 2017

Keywords

HDAC inhibitor
Hydroxamic acid
Linker
Solid-phase synthesis

Access to Document

10.1021/acscombsci.7b00068

OpenUrl availability

Full text

Cite this

Bang, C. G., Jensen, J. F., Cohrt, A. E. OH., Olsen, L. B., Siyum, S. G., Mortensen, K. T., Skovgaard, T., Berthelsen, J., Yang, L., Givskov, M., Qvortrup, K., & Nielsen, T. E. (2017). A Linker for the Solid-Phase Synthesis of Hydroxamic Acids and Identification of HDAC6 Inhibitors. A C S Combinatorial Science, 19(10), 657-669. https://doi.org/10.1021/acscombsci.7b00068

@article{0c64806d137e4538a2c29006c5bb117d,

title = "A Linker for the Solid-Phase Synthesis of Hydroxamic Acids and Identification of HDAC6 Inhibitors",

abstract = "We herein present broadly useful, readily available and nonintegral hydroxylamine linkers for the routine solid-phase synthesis of hydroxamic acids. The developed protocols enable the efficient synthesis and release of a wide range of hydroxamic acids from various resins, relying on high control and flexibility with respect to reagents and synthetic processes. A trityl-based hydroxylamine linker was used to synthesize a library of peptide hydroxamic acids. The inhibitory effects of the compounds were examined for seven HDAC enzyme subtypes using a chemiluminescence-based assay.",

keywords = "HDAC inhibitor, Hydroxamic acid, Linker, Solid-phase synthesis",

author = "Bang, {Claus Gunnar} and Jensen, {Jakob Feldthusen} and Cohrt, {Anders Emil O'Hanlon} and Olsen, {Lasse Bohn} and Siyum, {Saba Gebremedhin} and Mortensen, {Kim Thollund} and Tine Skovgaard and Jens Berthelsen and Liang Yang and Michael Givskov and Katrine Qvortrup and Nielsen, {Thomas Eiland}",

year = "2017",

doi = "10.1021/acscombsci.7b00068",

language = "English",

volume = "19",

pages = "657--669",

journal = "A C S Combinatorial Science",

issn = "2156-8952",

publisher = "ACS Publications",

number = "10",

}

TY - JOUR

T1 - A Linker for the Solid-Phase Synthesis of Hydroxamic Acids and Identification of HDAC6 Inhibitors

AU - Bang, Claus Gunnar

AU - Jensen, Jakob Feldthusen

AU - Cohrt, Anders Emil O'Hanlon

AU - Olsen, Lasse Bohn

AU - Siyum, Saba Gebremedhin

AU - Mortensen, Kim Thollund

AU - Skovgaard, Tine

AU - Berthelsen, Jens

AU - Yang, Liang

AU - Givskov, Michael

AU - Qvortrup, Katrine

AU - Nielsen, Thomas Eiland

PY - 2017

Y1 - 2017

N2 - We herein present broadly useful, readily available and nonintegral hydroxylamine linkers for the routine solid-phase synthesis of hydroxamic acids. The developed protocols enable the efficient synthesis and release of a wide range of hydroxamic acids from various resins, relying on high control and flexibility with respect to reagents and synthetic processes. A trityl-based hydroxylamine linker was used to synthesize a library of peptide hydroxamic acids. The inhibitory effects of the compounds were examined for seven HDAC enzyme subtypes using a chemiluminescence-based assay.

AB - We herein present broadly useful, readily available and nonintegral hydroxylamine linkers for the routine solid-phase synthesis of hydroxamic acids. The developed protocols enable the efficient synthesis and release of a wide range of hydroxamic acids from various resins, relying on high control and flexibility with respect to reagents and synthetic processes. A trityl-based hydroxylamine linker was used to synthesize a library of peptide hydroxamic acids. The inhibitory effects of the compounds were examined for seven HDAC enzyme subtypes using a chemiluminescence-based assay.

KW - HDAC inhibitor

KW - Hydroxamic acid

KW - Linker

KW - Solid-phase synthesis

U2 - 10.1021/acscombsci.7b00068

DO - 10.1021/acscombsci.7b00068

M3 - Journal article

C2 - 28746804

SN - 2156-8952

VL - 19

SP - 657

EP - 669

JO - A C S Combinatorial Science

JF - A C S Combinatorial Science

IS - 10

ER -

A Linker for the Solid-Phase Synthesis of Hydroxamic Acids and Identification of HDAC6 Inhibitors

Abstract

Keywords

Access to Document

OpenUrl availability

Fingerprint

Cite this