In vitro metabolic stability of iodinated obestatin peptides

Peptides. 2012 Feb;33(2):272-8. doi: 10.1016/j.peptides.2011.12.010. Epub 2011 Dec 27.

Abstract

Different iodinated mouse obestatin peptides have been characterized toward their in vitro stability in the main metabolic compartments plasma, liver and kidney. Using HPLC-UV for quantification, significant differences in the degradation kinetics of the iodinated peptides, arising from both enzymatic proteolysis and dehalogenation, were found when compared to the native, unmodified peptide. HPLC-MS/MS analysis demonstrated that the cleavage sites were dependent upon the biological matrix and the location of the amino acid residue incorporating the iodine atom(s). The degrading proteases were found to target peptide bonds further away from the iodine incorporation, while proteolytic cleavages of nearby peptide bonds were more limited. Diiodinated amino acid residue containing peptides were found to be more susceptible to deiodination than the mono-iodinated derivative. In plasma, the percentage of peptide degradation solely attributed to deiodinase activity after 20 min incubation reached up to 25% for 2,5-diiodo-H(19)-obestatin compared to 20% and only 3% for (3,5-diiodo-Y(16))- and (3-iodo-Y(16)) obestatin, respectively. Hence, our results demonstrate that the different iodinated peptides pose significantly different metabolization properties and thus, also different biological activities are expected for peptides upon iodination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Biotransformation
  • Chromatography, High Pressure Liquid
  • Half-Life
  • Iodine / metabolism*
  • Iodine Radioisotopes
  • Isotope Labeling
  • Kidney / metabolism
  • Kinetics
  • Liver / metabolism
  • Mice
  • Molecular Sequence Data
  • Peptide Hormones / metabolism*
  • Peptide Hydrolases / metabolism
  • Plasma
  • Protein Stability
  • Proteolysis
  • Tandem Mass Spectrometry
  • Tissue Extracts / metabolism*

Substances

  • Iodine Radioisotopes
  • Peptide Hormones
  • Tissue Extracts
  • obestatin, mouse
  • Iodine
  • Peptide Hydrolases