Enzyme inhibitor pepsin

Free Energy Calculations on Enzyme-Inhibitor Complexes Studies of Thermolysin and Rhizopus Pepsin... 

The mutation of the hydroxyl group positioned in R-configuration at the C(3) atom of the central statine (rSta) residue of the inhibitor gives rise to AAGbind of -0.51 kcal/mol, which is very close to the experimental value of -0.8 kcal/mol. It may be noted here that the starting configuration of the inhibitor in the enzyme-inhibitor complex is the same as that of pepstatin. The crystal structure of rhizopus pepsin or any other aspartic proteinase... 

There are also enzyme inhibitors used as defenses by an organism. Pepsin and trypsin inhibitors are found in the pancreas and keep the pancreas from being digested by its own enzymes. Some enzyme inhibitors also act as antibodies against microbial infections (see Section 6.20.3). 

As indicated, this paper will concentrate mainly on questions related to stability of enzyme inhibitor proteins and lectins. In particular, differential scanning calorimetric findings on effects of specific interactions on thermal stability will be reviewed. Stabilities of these proteins to other denaturing agents are not considered here. Older work showed that proteinase inhibitors are generally highly stable some resist denaturation at 100 C when dry or in neutral or weakly acidic solutions. Some even survive the action of pepsin, and can thus reach the small intestine intact. 

The diazomethyl ketone functional group was first observed to be an affinity label by Buchanan and co-workers who showed that the antibiotic azaserine, an O-diazoacetyl derivative, 9 inhibited an enzyme in the biosynthesis of purine by alkylation of a cysteine residue. 10 The acid protease pepsin was then observed to be inhibited by peptidyl diazomethyl ketones in the presence of copper ions with the resulting esterification of an aspartate residue. 11 Two peptidyl diazomethyl ketones, Z-Phe-CHN2 and Z-Phe-Phe-CHN2, were found to irreversibly inactivate papain, a cysteine protease. 12 Since these reports, many peptidyl diazomethyl ketones have been prepared primarily as inhibitors of various cysteine proteases. 7 Peptidyl diazomethyl ketones are also synthetic intermediates and have been used to prepare chloromethyl ketones (Section 15.1.3), 13 bromomethyl ketones (Section 15.1.3), acyloxymethyl ketones, 14 and (i-peptides. 15 A few peptidyl diazoalkyl ketones have been reported. 16,17 ... 

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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