Synthesis and in vivo lead detoxification evaluation of Poly-α,β-dl-aspartyl-l-methionine

Chem Res Toxicol. 2012 Feb 20;25(2):471-7. doi: 10.1021/tx2005037. Epub 2012 Feb 7.

Abstract

To increase the metal selectivity of polyaspartic acid, a so-called green chelant, poly-α,β-dl-aspartyl-l-methionine (PDM) was synthesized as a novel lead chelating agent. The phosphoric acid (80%) catalyzed thermal poly condensation of dl-aspartic acid provided poly succinimide, which was amidated with l-methionine to form PDM (MW: 29161). At the doses of 0.1, 1.0, and 10.0 nmol/kg, either by intraperitoneal injection (i.p.) or oral administration, PDM removed Pb from the spleens, hearts, and kidneys of mice, especially dose-dependently decreasing the accumulation of Pb in the brains, livers, and femurs of the mice, and did not interfere with the essential metals, including Cu, Fe, Mn, and Ca. Even at the dose of 0.1 nmol/kg, the i.p. injection of PDM removed Pb from the spleens, hearts, and kidneys of mice and increased the amount of urinary volume and urinary Pb, and the amount of fecal matter and the amount of fecal Pb, resulting in effective removal of Pb from the body of mice given Pb by i.p. injection. Our findings revealed that in aqueous solution PDM formed diverse nanospecies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism
  • Chelating Agents / pharmacology*
  • Environmental Pollutants / blood
  • Environmental Pollutants / pharmacokinetics*
  • Feces / chemistry
  • Femur / metabolism
  • Kidney / metabolism
  • Lead / blood
  • Lead / pharmacokinetics*
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred ICR
  • Myocardium / metabolism
  • Peptides / chemical synthesis
  • Peptides / pharmacology*
  • Spleen / metabolism

Substances

  • Chelating Agents
  • Environmental Pollutants
  • Peptides
  • poly-alpha,beta-dl-aspartyl-L-methionine
  • Lead