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Prodrugs of dynemicin analogs for selective chemotherapy mediated by an aldolase catalytic Ab

Academic Article
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Overview

authors

  • Sinha, Subhash
  • Li, L. S.
  • Miller, G. P.
  • Dutta, S.
  • Rader, Christoph
  • Lerner, Richard

publication date

  • March 2004

journal

  • Proceedings of the National Academy of Sciences of the United States of America  Journal

abstract

  • Prodrugs of dynemicin analogs were synthesized, and their activation by aldolase antibody (Ab) 38C2 was evaluated by DNA-cleaving activity, as well as tumor cell growth inhibition. Further, we provide evidence that the activated enediynes underwent covalent crosscoupling with the aldolase Ab, which appears to be a limiting factor of their tumor cell growth-inhibiting activity and should be of general interest in the field of enediyne chemotherapy. These findings might open new avenues for defined conjugations of small molecule drugs to mAbs in general and aldolase Abs in particular.

subject areas

  • Anthraquinones
  • Antibiotics, Antineoplastic
  • Antibodies, Catalytic
  • Cell Division
  • Cell Line, Tumor
  • Colonic Neoplasms
  • Drug Design
  • Fructose-Bisphosphate Aldolase
  • Humans
  • Indicators and Reagents
  • Mass Spectrometry
  • Prodrugs
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Identity

PubMed Central ID

  • PMC365749

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.0307319101

PubMed ID

  • 14981258
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Additional Document Info

start page

  • 3095

end page

  • 3099

volume

  • 101

issue

  • 9

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