Amine-catalyzed hydrolyses of cyclodextrin cinnamates

Komiyama, Makoto; Bender, Myron L.

doi:10.1073/pnas.73.9.2969

Cited by 7 publications

(2 citation statements)

References 11 publications

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“…Accordingly, in the effective transition state of the reaction governed by k cat /K m , a partial bond-making between the Cys-25 sulfur atom and the carbonyl carbon of the scissile bond occurs, while the double-bond character of the carbonyl carbon atom-carbonyl oxygen atom bond of the substrate, is partially reduced. Except for the relations k cat /K m ) k 1 and K S ) k 2 /k 1 found in this work, the last conclusion is supported also by previous ones suggested by others for serine proteases exhibiting k 2 /K S ) k 1 (or k cat /K m ) k 1 ) (25,43,44). Moreover, Angelides and Fink (45) have reported an irreversible reaction step observed before the formation of the acylenzyme during the hydrolysis of N R -carbobenzoxy-L-lysine methyl ester by papain at subzero temperatures.…”

Section: Discussionsupporting

confidence: 90%

Insight into the Catalysis of Hydrolysis of Four Newly Synthesized Substrates by Papain: A Proton Inventory Study

et al. 2001

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We synthesized the following four new peptide substrates, Suc-Phe-Leu-pNA, Suc-Phe-Leu-NMec, Suc-Phe-Leu-ONPh, and Pht-Phe-Leu-pNA, and we applied the proton inventory method to their hydrolysis by papain. Useful relationships between the rate constants of the catalytic reaction have been established and contributed to the elucidation of the hydrolytic mechanism of papain. For all amide substrates, the parameter K(S) and the rate constants k(1), k(-)(1), and k(2) were estimated. Moreover, it was found that k(cat)/K(m) = k(1) for all four substrates, while two exchangeable hydrogenic sites, one in the ground state and another in the transition state, generate an inverse isotope effect during the reaction governed by this parameter. The proton inventories of both k(2) and k(3) are essentially linear, whatever the acyl moiety and/or the leaving group of the substrate. The proton inventories of K(S) are also essentially linear for all amide substrates, while the observed large isotope effect of about 3 to 9 originates from a single hydrogenic site in the product state. This latter, in agreement to both the small transition state fractionation factors found for k(cat)/K(m) (or k(1)) and the unit ground-state fractionation factors found for k(2), argues for the formation of a tetrahedral adduct during the reaction governed by the k(1) parameter. Furthermore, papain acts as a one-proton catalyst during acylation or deacylation, both of which proceed through similar concerted reaction pathways, where a nucleophilic attack is accompanied by the movement of one proton.

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Section: Discussionsupporting

confidence: 90%

Insight into the Catalysis of Hydrolysis of Four Newly Synthesized Substrates by Papain: A Proton Inventory Study

et al. 2001

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“…Bender showed that CDs can accelerate many kinds of chemical reactions such as cleavage of esters, amides, organophosphates, carbonates or sulfates, intramolecular acyl migration, and decarboxylation. ,, Cyclodextrin-catalyzed reactions showed many of the kinetic features shown by enzymatic reactions including saturation, stereospecific catalyzes, and d , l -specificity, as well as substrate–catalyst complex formation and competitive inhibition. Bender concluded that CDs can serve as models of certain enzymes and classified the reactions in two categories: covalent catalysis in which CDs catalyze reactions via formation of covalent intermediates and noncovalent catalysis in which CDs provide their cavities as apolar or sterically restricted reaction fields without the formation of any covalent intermediates.…”

Section: The Period Of Application: From 1970 Until Nowmentioning

confidence: 99%