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Fluorescent cocaine probes: A tool for the selection and engineering of therapeutic antibodies

Academic Article
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Overview

related to degree

  • Kaufmann, Gunnar, Ph.D. in Chemistry, Scripps Research 2001 - 2006
  • Moss, Jason, Ph.D. in Chemistry, Scripps Research 2000 - 2005

authors

  • Meijler, M. M.
  • Kaufmann, Gunnar
  • Qi, L. W.
  • Mee, J. M.
  • Coyle, A. R.
  • Moss, Jason
  • Wirsching, P.
  • Matsushita, M.
  • Janda, Kim

publication date

  • March 2005

journal

  • Journal of the American Chemical Society  Journal

abstract

  • Cocaine is a highly addictive drug, and despite intensive efforts, effective therapies for cocaine craving and addiction remain elusive. In recent years, we and others have reported advances in anti-cocaine immunopharmacotherapy based on specific antibodies capable of sequestering the drug before it reaches the brain. In an effort to obtain high affinity therapeutic anti-cocaine antibodies, either whole IgGs or other antibody constructs, fluorescence spectroscopic techniques could provide a means of assisting selection and engineering strategies. We report the synthesis of a series of cocaine-fluorophore conjugates (GNC-F1, GNC-F2, GNC-I) and the functional evaluation of these compounds against single-chain Fv antibodies obtained via crystallographic analysis/engineering and against commercially available anti-cocaine monoclonal antibodies with a wide range of cocaine-binding affinities. From these studies, we determined that the GNC-F2 fluorophore reproduced affinity constants obtained using [(3)H]-labeled cocaine. We anticipate that the readily synthesized and nonradioactive GNC-F2 will find use both as a tool for bioimaging and in the high-throughput selection and engineering of potential therapeutic antibodies against cocaine.

subject areas

  • Animals
  • Antibodies, Monoclonal
  • Base Sequence
  • Cocaine
  • Fluorescent Dyes
  • Humans
  • Immunoconjugates
  • Immunoglobulin Fragments
  • Immunoglobulin G
  • Kinetics
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Peptide Library
  • Protein Engineering
  • Spectrometry, Fluorescence
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Identity

International Standard Serial Number (ISSN)

  • 0002-7863

Digital Object Identifier (DOI)

  • 10.1021/ja043935e

PubMed ID

  • 15725002
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Additional Document Info

start page

  • 2477

end page

  • 2484

volume

  • 127

issue

  • 8

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