H-1-NMR RELAXOMETRIC STUDY OF PANCREATIC SERINE (PRO)ENZYME INHIBITION BY A GD(III) CHELATE BEARING BORONIC FUNCTIONALITIES

Binding of the paramagnetic N,N xyphenylcarbamoylmethyl)-diethylenetri amine-N,N',N ''-triacetic acid Gd(III) complex (GdBB) to chymotrypsin, chymotrypsinogen, trypsin, trypsinogen and pancreatic elastase has be en investigated by H-1-NMR relaxometry, between pH 6.0 and 8.5, at 25. 0 degrees C. Values of K-i for the competitive inhibition of serine pr oteinases by GdBB are in excellent agreement with values of K-d obtain ed by H-1-NMR relaxometry, suggesting that the substrate and the param agnetic complex bind to the same region. Moreover, H-1-NMR relaxometry allowed to deter mine values of K-d for GdBB binding to chymotrypsino gen and trypsinogen, both devoid of catalytic activity. The increase o f the water proton relaxation rats upon GdBB binding to serine (pro)en zymes may be useful in the design of novel functional contrast agents for magnetic resonance imaging.