Expression and purification recombinant antihypertensive peptide ameliorates hypertension in rats with spontaneous hypertension

Protein Expr Purif. 2015 Sep:113:30-4. doi: 10.1016/j.pep.2015.05.001. Epub 2015 May 8.

Abstract

A highly efficient Escherichia coli expression system was established to obtain an appreciable quantity of antihypertensive peptide. The DNA-coding sequence for the Gly-Val-Tyr-Pro-His-Lys peptide was chemically synthesized and linked to form a ten-copy in tandem. It was cloned into the vector pET-15b and expressed in E. coli BL21 (DE3). The optimal conditions for maximal expression were verified and included the induction time and the concentration of isopropyl-β-D-thiogalactopyranoside. The recombinant protein was purified by affinity chromatography to greater than 95% purity, and further purification was achieved by High-performance Liquid Chromatography after cleavage with trypsin. The product was identified by Electrospray Ionization-Mass Spectrometry. The antihypertensive effects of the recombinant AHP were investigated in spontaneously hypertensive rats. The in vivo results demonstrated that a single oral administration of this peptide in spontaneously hypertensive rats resulted in a significant reduction of systolic blood pressure at 2h. Systolic blood pressure was stabilized 4h later and remained at a low level for 24h. This study provides a practical method to develop the peptide into functional foods or drugs for the prevention and treatment of hypertension.

Keywords: Antihypertensive peptide; Expression; Hypertension; Purification; Tandem.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antihypertensive Agents / chemistry
  • Antihypertensive Agents / isolation & purification
  • Antihypertensive Agents / metabolism*
  • Antihypertensive Agents / pharmacology*
  • Base Sequence
  • Blood Pressure / drug effects
  • Hypertension / physiopathology*
  • Molecular Sequence Data
  • Oligopeptides / chemistry
  • Oligopeptides / isolation & purification
  • Oligopeptides / metabolism
  • Oligopeptides / pharmacology
  • Rats
  • Rats, Inbred SHR
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / isolation & purification
  • Recombinant Fusion Proteins / metabolism*
  • Recombinant Fusion Proteins / pharmacology*

Substances

  • Antihypertensive Agents
  • Oligopeptides
  • Recombinant Fusion Proteins
  • C111 peptide