Publications by authors named "Eduardo J Martinez"

2 Publications

  • Page 1 of 1

Using 'biased-privileged' scaffolds to identify lysine methyltransferase inhibitors.

Bioorg Med Chem 2014 Apr 28;22(7):2253-60. Epub 2014 Feb 28.

Laboratory of Chemistry and Cell Biology, Rockefeller University, New York, NY 10065, USA. Electronic address:

Methylation of histones by lysine methyltransferases (KMTases) plays important roles in regulating chromatin function. It is also now clear that improper KMTases activity is linked to human diseases, such as cancer. We report an approach that employs drug-like 'privileged' scaffolds biased with motifs present in S-adenosyl methionine, the cofactor used by KMTases, to efficiently generate inhibitors for Set7, a biochemically well-characterized KMTase. Setin-1, the most potent inhibitor of Set7 we have developed also inhibits the KMTase G9a. Together these data suggest that these inhibitors should provide good starting points to generate useful probes for KMTase biology and guide the design of KMTase inhibitors with drug-like properties.
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http://dx.doi.org/10.1016/j.bmc.2014.02.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4038709PMC
April 2014

Integrating transcriptional and metabolite profiles to direct the engineering of lovastatin-producing fungal strains.

Nat Biotechnol 2003 Feb 21;21(2):150-6. Epub 2003 Jan 21.

Microbia, Inc., 320 Bent Street, Cambridge, MA 02141, USA.

We describe a method to decipher the complex inter-relationships between metabolite production trends and gene expression events, and show how information gleaned from such studies can be applied to yield improved production strains. Genomic fragment microarrays were constructed for the Aspergillus terreus genome, and transcriptional profiles were generated from strains engineered to produce varying amounts of the medically significant natural product lovastatin. Metabolite detection methods were employed to quantify the polyketide-derived secondary metabolites lovastatin and (+)-geodin in broths from fermentations of the same strains. Association analysis of the resulting transcriptional and metabolic data sets provides mechanistic insight into the genetic and physiological control of lovastatin and (+)-geodin biosynthesis, and identifies novel components involved in the production of (+)-geodin, as well as other secondary metabolites. Furthermore, this analysis identifies specific tools, including promoters for reporter-based selection systems, that we employed to improve lovastatin production by A. terreus.
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http://dx.doi.org/10.1038/nbt781DOI Listing
February 2003