Use of PROTACS as molecular probes of angiogenesis

Paola Bargagna-Mohan; Sun Hee Baek; Hyosung Lee; Kyungbo Kim; Royce Mohan

doi:10.1016/j.bmcl.2005.04.008

Use of PROTACS as molecular probes of angiogenesis

Paola Bargagna-Mohan, Sun Hee Baek, Hyosung Lee, Kyungbo Kim, Royce Mohan

Pharmaceutical Sciences

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

57 Scopus citations

Abstract

Small molecules designed to specifically activate or inactivate protein functions have been useful to study biological processes. PROTACS are small molecule chimera which comprise a ligand and a peptide recognition motif for an E3 ligase. These novel reagents exploit the ubiquitin-mediated proteasome degradation pathway to target the ligand-bound protein for intracellular degradation. Here, we report that an estrogen receptor (ER)-targeting PROTACS that causes degradation of ER is able to potently inhibit endothelial cell differentiation in a three-dimensional angiogenic sprouting assay. These findings support the use of ER-targeting PROTACS as probes of angiogenesis.

Original language	English
Pages (from-to)	2724-2727
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	15
Issue number	11
DOIs	https://doi.org/10.1016/j.bmcl.2005.04.008
State	Published - Jun 2 2005

Bibliographical note

Funding Information:
We are grateful to the Department of Ophthalmology and Visual Sciences (University of Kentucky) for generous start-up funds to R.M. and the Kentucky Lung Cancer Research Program for financial support to K.K.

Funding

We are grateful to the Department of Ophthalmology and Visual Sciences (University of Kentucky) for generous start-up funds to R.M. and the Kentucky Lung Cancer Research Program for financial support to K.K.

Funders	Funder number
Kentucky Lung Cancer Research Program
National Eye Institute (NEI)	R01EY016782
University of Kentucky

Keywords

Angiogenesis
Endothelial cell differentiation
Estrogen
PROTACS
Receptor

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2005.04.008

Cite this

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abstract = "Small molecules designed to specifically activate or inactivate protein functions have been useful to study biological processes. PROTACS are small molecule chimera which comprise a ligand and a peptide recognition motif for an E3 ligase. These novel reagents exploit the ubiquitin-mediated proteasome degradation pathway to target the ligand-bound protein for intracellular degradation. Here, we report that an estrogen receptor (ER)-targeting PROTACS that causes degradation of ER is able to potently inhibit endothelial cell differentiation in a three-dimensional angiogenic sprouting assay. These findings support the use of ER-targeting PROTACS as probes of angiogenesis.",

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author = "Paola Bargagna-Mohan and Baek, {Sun Hee} and Hyosung Lee and Kyungbo Kim and Royce Mohan",

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AU - Bargagna-Mohan, Paola

AU - Baek, Sun Hee

AU - Lee, Hyosung

AU - Kim, Kyungbo

AU - Mohan, Royce

N1 - Funding Information: We are grateful to the Department of Ophthalmology and Visual Sciences (University of Kentucky) for generous start-up funds to R.M. and the Kentucky Lung Cancer Research Program for financial support to K.K.

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Y1 - 2005/6/2

N2 - Small molecules designed to specifically activate or inactivate protein functions have been useful to study biological processes. PROTACS are small molecule chimera which comprise a ligand and a peptide recognition motif for an E3 ligase. These novel reagents exploit the ubiquitin-mediated proteasome degradation pathway to target the ligand-bound protein for intracellular degradation. Here, we report that an estrogen receptor (ER)-targeting PROTACS that causes degradation of ER is able to potently inhibit endothelial cell differentiation in a three-dimensional angiogenic sprouting assay. These findings support the use of ER-targeting PROTACS as probes of angiogenesis.

AB - Small molecules designed to specifically activate or inactivate protein functions have been useful to study biological processes. PROTACS are small molecule chimera which comprise a ligand and a peptide recognition motif for an E3 ligase. These novel reagents exploit the ubiquitin-mediated proteasome degradation pathway to target the ligand-bound protein for intracellular degradation. Here, we report that an estrogen receptor (ER)-targeting PROTACS that causes degradation of ER is able to potently inhibit endothelial cell differentiation in a three-dimensional angiogenic sprouting assay. These findings support the use of ER-targeting PROTACS as probes of angiogenesis.

KW - Angiogenesis

KW - Endothelial cell differentiation

KW - Estrogen

KW - PROTACS

KW - Receptor

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Use of PROTACS as molecular probes of angiogenesis

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

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