title: Effect of Inhibiting Histone Deacetylase with Short-Chain Carboxylic Acids and Their Hydroxamic Acid Analogs on Vertebrate Development and Neuronal Chromatin.
abstract: Carboxylic acids with known central nervous system and histone deacetylase (HDAC) inhibitory activities were converted to hydroxamic acids and tested using a suite of in vitro biochemical assays with recombinant HDAC isoforms, cell based assays in human cervical carcinoma Hela cells and primary cultures from mouse forebrain, and a whole animal (Xenopus laevis) developmental assay. Relative to the parent carboxylic acids, two of these analogs exhibited enhanced potency, and one analog showed altered HDAC isoform selectivity and in vivo activity in the Xenopus assay. We discuss potential uses of these novel hydroxamic acids in studies aimed at determining the utility of HDAC inhibitors as memory enhancers and mood stabilizers.
authors.affiliation: Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, MA 02142, USA.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Fass
authors.forename: Rishita
authors.initials: R
authors.lastname: Shah
authors.forename: Balaram
authors.initials: B
authors.lastname: Ghosh
authors.forename: Krista
authors.initials: K
authors.lastname: Hennig
authors.forename: Stephanie
authors.initials: S
authors.lastname: Norton
authors.forename: Wen-Ning
authors.initials: WN
authors.lastname: Zhao
authors.forename: Surya A
authors.initials: SA
authors.lastname: Reis
authors.forename: Peter S
authors.initials: PS
authors.lastname: Klein
authors.forename: Ralph
authors.initials: R
authors.lastname: Mazitschek
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Maglathlin
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Lewis
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Haggarty