Suicide reagent

Herbicidal Inhibition of Enzymes. The Hst of known en2yme inhibitors contains five principal categories group-specific reagents substrate or ground-state analogues, ie, rapidly reversible inhibitors affinity and photo-affinity labels suicide substrate, or inhibitors and transition-state, or reaction-intermediate, analogues, ie, slowly reversible inhibitors (106). 

In the preceding section, four diagnostic tests of affinity labeling were listed (inactivation inhibited by substrates, pH dependence of inactivation similar to that of catalysis, labeled inhibitor covalently bound in 1 1 stoichiometry, and saturation kinetics obeyed). The same criteria may be used to diagnose suicide inhibition. In addition, tests must be made to detect any diffusion of the activated intermediate I into solution. For example, the addition of —SH reagents that rapidly react with electrophiles and hence scavenge them should not slow down the rate of reaction. The suicide inhibitor should not, in any case, react with the thiol at an appreciable rate in the absence of enzyme. 

Figure 14. Irreversible inactivation of E. coli p-hydroxydecanoyl thio-ester dehydrase by a suicide reagent, A(3 4)-decanoyl N-acetyl cysteamine...

Perhaps the toxoid research programs now being carried out in many research laboratories will provide a wide spectrum of toxoids for many different infectious diseases. Most of these toxoids should be prepared by specific-affinity-type reagents, including the suicide type, for the offending toxin from bacterial or viral agents. 

These "suicide reagents" will be described in detail elsewhere in this volume (44), so only one phase will be briefly mentioned here. Of particular interest to food and nutrition researchers are the naturally occurring toxins which involve a "suicide" mechanism (42). Some of these can be consumed in foods or feeds and commonly occur in a number of different plant sources. A very common toxin is the beta-aminopropionitrile present in lathyritic legumes, and another is the wildfire toxin (42) (Figure 21). 

A suicide reagent is a substrate, or a substance similar to a substrate, which is acted upon by the enzyme. Catalytic conversion pro-... 

Suberic acid, 506 Substrate analogs, 8, 9 Subtilisin, 22, 27, 75, 206, 207 Subtilisin BPN, 215 Succinimide esters, 96 Sucrase-isomaltase complex, 377,379 Suicide reagents, 9, 10 Sulfonyl azides, 78 a-Sulfonyl nitrenes, 78 Sulfoxides, 135... 

---