Development of an enzyme immunoassay for a stable amidated analog of the hemoregulatory peptide acetyl-Ser-Asp-Lys-Pro

J Immunoassay Immunochem. 2001;22(1):15-31. doi: 10.1081/IAS-100102895.

Abstract

The tetrapeptide Acetyl-Ser-Asp-Lys-Pro (AcSDKP) has been shown to protect hematopoietic stem cells from the toxicity of anticancer chemotherapies. Since its pharmacological efficacy is limited by a rapid degradation by Angiotensin-I Converting Enzyme (ACE), AcSDKP analogs resistant to ACE have been synthesized. One of these compounds (AcSDKP-NH,) differs from the native AcSDKP by amidation of the C-terminus. Further evaluations of this molecule require an analytical method in order to characterize its pharmacokinetic profile. We report, here, the development of a highly specific and sensitive enzyme immunoassay (EIA) for AcSDKP-NH, thatdoes not cross-react with endogenous or exogenous AcSDKP. Using AcSDKP-NH2-acetylcholinesterase conjugate as a tracer, rabbit specific antiserum and microtiter plates coated with goat anti-rabbit immunoglobulins, this EIA allows the determination of AcSDKP-NH2 with limits of quantitation of 1 nM in mouse plasma and 100 pmol/g in tissues. Intra-day and inter-day coefficients of variations were less than 20%. The method was successfully applied to a pharmacokinetic study in order to compare plasma and tissue profiles of AcSDKP-NH2 and AcSDKP. Plasma AcSDKP-NH2 levels were found higher than those of AcSDKP, with AUCinf and Cmax values, respectively, 26- and 10-fold higher than that of AcSDKP.

MeSH terms

  • Amides / chemistry*
  • Animals
  • Humans
  • Immune Sera
  • Immunoenzyme Techniques / methods*
  • Mice
  • Mice, Inbred CBA
  • Oligopeptides / analysis*
  • Oligopeptides / chemistry
  • Oligopeptides / pharmacokinetics
  • Protein Conformation
  • Reproducibility of Results
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Substances

  • Amides
  • Immune Sera
  • Oligopeptides
  • goralatide