Transition State Differences between Amides and Esters in Chymotrypsin-Catalyzed Hydrolysis

pH-dependence and structure–activity relationships in the papain-catalysed hydrolysis of anilides

“…kc,.t.IKm for the a-chymotrypsincatalysed hydrolysis of the more specific aryl hippurates and aryl N-mesyl-L-phenylalaninates has Hammett p values of+0.5 and +0.45 respectively (Williams, 1970). The ac-chymotrypsin-catalysed hydrolysis of the aniides of N-benzoyl-L-tyrosine (Sager & Parks, 1963) and N-acetyl-L-tyrosine (Inagami, York & Patchornik, 1965), however, have p values of -1.63 and -2.0 respectively for the acylation constant, suggesting that catalysis of the acylation step also involves an electrophilic component. Most probably this takes the form of acid catalysis, either by pretransition-state proton transfer (Wang & Parker, 1967;Parker & Wang, 1968;Wang, 1968) or by general-acid catalysis (Caplow, 1969).…”

“…kcat. (s-') Km ( anilides of N-benzoyl-L-tyrosine (-1.63) and N-acetyl-L-tyrosine (-2.0) (Sager & Parks, 1963;Inagami et al 1965) compared with those for the papain-catalysed hydrolysis of substrates with similar leaving groups suggests that the bondbreaking and bond-making processes are probably catalysed chemically by similar mechanisms, e.g. general-base-general-acid catalysis.…”

Chymotrypsin-Catalyzed Hydrolysis of m-, p-, and o-Nitroanilides of N-Benzoyl-L-tyrosine*

“…The results of these studies indicate a difference in the response of phenol ester and anilide substrates to changes in charge density at the reaction site. Bender and Nakamura (1962), in an investigation of substituent effects, have shown that electron withdrawal facilitates the acylation of chymotrypsin by phenol esters, while other investigators have found that electron-donating substituents facilitate the acylation of chymotrypsin by A-benzoyl-and iV-acetyl-L-tyrosine anilides (Sager and Parks, 1963;Inagami et al, 1965).…”

Kinetics and mechanism of the reaction of 2,2'-dichlorodiethylamine with aqueous carbon dioxide

“…The agreement between this value and that which was determined directly by pH titrations on 2,2'-dichlorodiethylamine, (3.9 ± 0.4) X 10-7 mol l.-1, is excellent evidence that the rate-controlling step in the formation of the oxazolidinone is ring closure from the carbamate anion. The intercept of a plot of l/k' vs. 1/[C02] (eq 15) is expressed by eq 17. When the intercept is plotted intercept _1 ks [h+] + m + tH+J2 k.lCB -k\ k. ¡k _ (17) against the hydrogen ion concentration (Figure 3) the intercept of the resulting line provides a value for ks = (2.4(+5.3, -1.0)) X 10-2 sec-1.…”