Title
Bisubstrate analogue structure-activity relationships for p300 histone acetyltransferase inhibitors
UMMS Affiliation
Department of Biochemistry and Molecular Pharmacology
Publication Date
2004-06-15
Document Type
Article
Subjects
Acetyltransferases; Cell Cycle Proteins; Coenzyme A; Enzyme Inhibitors; Histone Acetyltransferases; Lysine; Molecular Structure; Structure-Activity Relationship; Transcription Factors; p300-CBP Transcription Factors
Disciplines
Biochemistry | Enzymes and Coenzymes | Medicinal-Pharmaceutical Chemistry | Therapeutics
Abstract
p300 and CBP are important histone acetyltransferases (HATs) that regulate gene expression and may be anti-cancer drug targets. Based on a previous lead compound, Lys-CoA, we have used solid phase synthesis to generate a series of 11 new analogues and evaluated these compounds as HAT inhibitors. Increased spacing between the CoA moiety and the lysyl moiety generally decreases inhibitory potency. We have found two substituted derivatives that show about 4-fold increased potency compared to the parent compound Lys-CoA. These structure-activity studies allow for a greater understanding of the optimal requirements for potent inhibition of HAT enzymes and pave the way for a novel class of anti-cancer therapeutics.
DOI of Published Version
10.1016/j.bmc.2004.03.070
Source
Bioorg Med Chem. 2004 Jun 15;12(12):3383-90. Link to article on publisher's site
Journal/Book/Conference Title
Bioorganic and medicinal chemistry
Related Resources
Repository Citation
Sagar, Vatsala; Zheng, Weiping; Thompson, Paul R.; and Cole, Philip A., "Bisubstrate analogue structure-activity relationships for p300 histone acetyltransferase inhibitors" (2004). Thompson Lab Publications. 83.
https://escholarship.umassmed.edu/thompson/83
Comments
At the time of publication, Paul Thompson was not yet affiliated with UMass Medical School.