Conjugate enzyme inhibitors, effect

Some boronic acid-based enzyme inhibitors undergo strong yet reversible covalent attachment to a nucleophile at the enzyme s active site, while others simply act as competitive inhibitors in their borate conjugate base form. Boronic acid-based inhibition of thrombin has been achieved <93MI109>, and that of P-lactamases has been particularly effective <95TL8399, 96M1688>. When compared to other covalent transition-state analog inhibitors of P-lactamases like phos-... 

Nevertheless, the use of bacitracin as an enzyme inhibitor in order to improve drug uptake in vivo remains questionable, because bacitracin-mediated nephrotoxicity has been reported previously (Drapeau et al. 1992). However, it was demonstrated recently that bacitracin can be covalently bond to a mucoadhesive, non-absorbable polymer and that this polymer-bacitracin conjugate still retains its inhibitory activity (Bernkop-Schnurch and Marschiitz 1997). The reason for using such a polymer-inhibitor conjugate instead of unmodified bacitracin is that the polymer-bacitracin conjugate is believed to remain in the GI tract which would exclude systemic side effects. More information about polymer-inhibitor conjugates are provided in Section 4.4.6.3 of this article. 

A very special case of toxicity by a sulfate conjugate Is the effect of ethanolamlno-0-sulfate, which Is an irreversible "suicide" Inhibitor of 4-aminobutyrate aminotransferase. This sulfate conjugate is a substrate analogue for the enzyme, which, because of the electronegativity of the sulfate group, is converted by 8-ellminatlon... 

The PL-catechin conjugate showed greatly amplified concentration-dependent inhibition activity against bacterial collagenase (ChC) on the basis of the catechin unit, which is considered to be due to effective multivalent interaction between ChC and the catechin unit in the conjugate. The kinetic study suggests that this conjugate is a mixed-type inhibitor for ChC. Hyaluronidase is an enzyme which catalyzes hydrolysis of hyaluronic acid and is often involved in a number... 

Both the 26S proteasome and the RC hydrolyze all four nucleotide triphosphates, with ATP and CTP preferred over GTP and UTP [58]. Although ATP hydrolysis is required for conjugate degradation, the two processes are not strictly coupled. Complete inhibition of the peptidase activity of the 26S proteasome by calpain inhibitor I has little effect on the ATPase activity of the enzyme. The nucleotidase activities of the RC and the 26S proteasome closely resemble those of E. coli Lon protease, which is composed of identical subunits that possess both proteolytic and nucleotidase activities in the same polypeptide chain. Like the regulatory complex and 26S proteasome, Lon hydrolyzes all four ribonucleotide triphosphates, but not ADP or AMP [18]. 

Sodium azide is a powerful inhibitor of HRP, but sodium azide can be used with alkaline phosphatase conjugated antibodies without harmful effects. In addition, tap water or water deionized with polystyrene resins may inactivate the enzyme conjugate. Only use distilled, deionized water Tween-20 may interfere with some antibody-antibody reactions or may wash the protein of interest off the membrane. Tween-20 may be left out of the washes, but this may result in increased background... 

For an intended drug uptake in the stomach, the only proteolytic enzyme which has to be inhibited is pepsin. It has been demonstrated that the polymeric pepsin-inhibitor conjugate chitosan-pepstatin was capable to efficiently protect the peptide drug calcitonin in the presence of pepsin. These results have been additionally confirmed in vivo. The administration of minitablets comprising of a mixture of calcitonin, chitosan, and chitosan-pepstatin to rats led to a reduction of the plasma calcium level, whereas no effect was observed when... 

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