Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form
As of April 1st VIVO Scientific Profiles will no longer updated for faculty, and the link to VIVO will be removed from the library website. Faculty profile pages will continue to be updated via Interfolio. VIVO will continue being used behind the scenes to update graduate student profiles. Please contact helplib@scripps.edu if you have questions.
How to download citations from VIVO | Alternative profile options

Asymmetric synthesis of inhibitors of glycinamide ribonucleotide transformylase

Academic Article
uri icon
  • Overview
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

related to degree

  • DeMartino, Jessica, Ph.D. in Chemistry, Scripps Research 2003 - 2008

authors

  • DeMartino, Jessica
  • Hwang, I.
  • Connelly, S.
  • Wilson, Ian
  • Boger, Dale

publication date

  • September 2008

journal

  • Journal of Medicinal Chemistry  Journal

abstract

  • Glycinamide ribonucleotide transformylase (GAR Tfase) catalyzes the first of two formyl transfer steps in the de novo purine biosynthetic pathway that require folate cofactors and has emerged as a productive target for antineoplastic therapeutic intervention. The asymmetric synthesis and evaluation of the two diastereomers of 10-methylthio-DDACTHF (10R-3 and 10S-3) and related analogues as potential inhibitors of GAR Tfase are reported. This work, which defines the importance of the C10 stereochemistry for this class of inhibitors of GAR Tfase, revealed that both diastereomers are potent inhibitors of rhGAR Tfase (10R-3 Ki = 210 nM, 10S-3 Ki = 180 nM) that exhibit effective cell growth inhibition (CCRF-CEM IC50 = 80 and 50 nM, respectively), which is dependent on intracellular polyglutamation by folylpolyglutamate synthetase (FPGS) but not intracellular transport by the reduced folate carrier.

subject areas

  • Antineoplastic Agents
  • Cell Line, Tumor
  • Cell Proliferation
  • Enzyme Inhibitors
  • Humans
  • Inhibitory Concentration 50
  • Peptide Synthases
  • Phosphoribosylglycinamide Formyltransferase
  • Stereoisomerism
  • Structure-Activity Relationship
scroll to property group menus

Identity

PubMed Central ID

  • PMC2559975

International Standard Serial Number (ISSN)

  • 0022-2623

Digital Object Identifier (DOI)

  • 10.1021/jm800555h

PubMed ID

  • 18686942
scroll to property group menus

Additional Document Info

start page

  • 5441

end page

  • 5448

volume

  • 51

issue

  • 17

©2022 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support