Ex Vivo Measurement of Enzyme Stability in Human Plasma: A Potential Screening Method for In Vivo Stability

Abstract

Previously, we assayed several phosphotriesterase (PTE) variants with increased activity on G-type chemical nerve agents and observed increased activity on the most toxic enantiomers. The purpose of this study is to determine the feasibility of the use of ex vivo plasma assays as a means of estimating the stability of enzymes that might be candidates for in vivo treatment. Activity measurements using wild-type (WT) PTE and several of its mutants on soman and cyclosarin after incubation in human plasma indicate that WT PTE and the YT mutant of that enzyme have comparable stability in plasma.

Open PDF

Document Details

Document Type
Technical Report
Publication Date
May 01, 2014
Accession Number
ADA601155

Entities

People

  • Mark A. Guelta
  • Melissa M. Dixon
  • Steven P. Harvey

Organizations

  • Edgewood Chemical Biological Center

Tags

Communities of Interest

  • Counter WMD

DTIC Thesaurus Topics

  • Antipersonnel Agents
  • Chemical Warfare Agents
  • Chemical Weapons
  • Degradation
  • Department Of Defense
  • Enantiomers
  • Enzymes
  • Fluorides
  • G Agents
  • Hydrolysis
  • Information Operations
  • Inoculation
  • Measurement
  • Nerve Agents
  • Poisoning
  • Spreadsheet Software
  • Substrates

Fields of Study

  • Biology

Readers

  • Analytical Chemistry
  • Molecular and Cellular Biochemistry
  • Toxicology/Environmental Toxicology