Pepsin inhibition

Carboxymethylthio derivatives of 1,3-dialkyl-6-aminouracils (LXIX) and their amides possess anti-inflammatory activity, as evidenced by their ability to inhibit local edema formation [434,435]. Bronchodilator and CNS stimulant activity are also claimed. The related 1-aryl derivatives (LXIX R = Ar) are reported to have anti-inflammatory, hypocholesterolemic, pepsin-inhibiting, and anti-ulcer properties [436]. 

The sulfate esters and sulfonate derivatives of polysaccharides and lignin form chemical complexes with the enzyme pepsin. These complexes have no proteolytic activity. Bc-cau.se polysulfatcs and polysulfonates arc ptxirly absorhol from the GI tract, specific chemical complexaiion appeals to be a desirable mechanism of pepsin inhibition. Unfoitu-nately. these polymers are also potent anticoagulants. 

Figure 5. The sequence of a pepsin-inhibiting peptide formed during the activation of porcine pepsinogen. The lower sequence illustrates the proposed binding mode with Leu-12 as the residue. Below each residue is listed whether that amino acid residue has positive (+), negative (-), or neutral (n) cleavage probabilities.

Assay of pepsin-inhibiting activity-The activity of the pepsin used was calculated on the basis of 81% of active pepsin by comparison of its hemoglobin-splitting activity with our purest pepsin preparation (10). 

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