1H-NMR relaxometric study of pancreatic serine (pro)enzyme inhibition by a Gd(III) chelate bearing boronic functionalities

Biochem Mol Biol Int. 1996 Jul;39(4):741-6. doi: 10.1080/15216549600201821.

Abstract

Binding of the paramagnetic N,N"-bis(m-boroxyphenylcarbamoylmethyl)-diethylenetriamine-N,N', N"-triacetic acid Gd(III) [sequence: see text] complex (GdBB) to chymotrypsin, chymotrypsinogen, trypsin, trypsinogen and pancreatic elastase has been investigated by 1H-NMR relaxometry, between pH 6.0 and 8.5, at 25.0 degrees C. Values of Ki for the competitive inhibition of serine proteinases by GdBB are in excellent agreement with values of Kd obtained by 1H-NMR relaxometry, suggesting that the substrate and the paramagnetic complex bind to the same region. Moreover, 1H-NMR relaxometry allowed to determine values of Kd for GdBB binding to chymotrypsinogen and trypsinogen, both devoid of catalytic activity. The increase of the water proton relaxation rate upon GdBB binding to serine (pro)enzymes may be useful in the design of novel functional contrast agents for magnetic resonance imaging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Boron*
  • Chymotrypsin / metabolism
  • Chymotrypsinogen / metabolism
  • Contrast Media*
  • Gadolinium DTPA
  • Magnetic Resonance Spectroscopy
  • Organometallic Compounds*
  • Pancreas / enzymology*
  • Pancreatic Elastase / metabolism
  • Pentetic Acid / analogs & derivatives*
  • Serine Proteinase Inhibitors / chemistry*
  • Trypsin / metabolism
  • Trypsinogen / metabolism

Substances

  • Contrast Media
  • Organometallic Compounds
  • Serine Proteinase Inhibitors
  • Pentetic Acid
  • Trypsinogen
  • Chymotrypsinogen
  • Chymotrypsin
  • Pancreatic Elastase
  • Trypsin
  • Gadolinium DTPA
  • Boron