Histidine-containing polymers

In the late 1950s it was shown that imidazole catalyzes the hydrolyses of />-nitrophenyl acetate (7, 76) and that histidine was at the active site of a-chymotrypsin (2). These findings led Katchalski ei al. (39) to synthesize a number of histidine-containing polymers for evaluation as catalysts. Second-order rate constants were calculated on the basis of the concentration of neutral imidazole, that is, k2 = (A bs — .)/a[IM], where k , is the rate constant in the absence of catalyst and a is the fraction ionized. Some of these rate constants appear in Table I. All of the polymers possess less than... 

In the area of catalysis, the esterolysis reactions of imidazole-containing polymers have been investigated in detail as possible models for histidine-containing hydrolytic enzymes such as a-chymotrypsin (77MI11104). Accelerations are observed in the rate of hydrolysis of esters such as 4-nitrophenyl acetate catalyzed by poly(4(5)-vinylimidazole) when compared with that found in the presence of imidazole itself. These results have been explained in terms of a cooperative or bifunctional interaction between neighboring imidazole functions (Scheme 19), although hydrophobic and electrostatic interactions may also contribute to the rate enhancements. Recently these interpretations, particularly that depicted in Scheme 19, have been seriously questioned (see Section 1.11.4.2.2). 

Substrate-catalyst interaction is also essential for micellar catalysis, the principles of which have long been established and consistently described in detail [63-66]. The main feature of micellar catalysis is the ability of reacting species to concentrate inside micelles, which leads to a considerable acceleration of the reaction. The same principle may apply for polymer systems. An interesting way to concentrate the substrate inside polymer catalysts is the use of cross-linked amphiphilic polymer latexes [67-69]. Liu et al. [67] synthesized a histidine-containing resin which was active in hydrolysis of p-nitrophenyl acetate (NPA). The kinetics curve of NPA decomposition in the presence of the resin was of Michaelis-Menten type, indicating that the catalytic act was accompanied by sorption of the substrate. However, no discussion of the possible sorption mechanisms (i.e., sorption by the interfaces or by the core of the resin beads) was presented. 

Imidazole is found in many enzymes as histidine residue. It plays a role of electron donor in biological systems. Imidazole is one of the nucleophiles, and many nucleophile-containing polymers have been synthesized as a mode of the enzyme such as a-chymotrypsin. 

Proteins are naturally occurring polymers of a-amino acids (Chapter 23). Three of the 20 most common naturally occurring amino acids contain heterocyclic rings Proline contains a pyrrolidine ring, tryptophan contains an indole ring, and histidine contains an imidazole ring. 

Imidazole-containing polymers designed on the basis of histidine have been reported to have a proton-sponge property and enhanced release of complexes into the cytoplasm following adsorptive pinocytosis [62]. 

This review article summarizes our more recent investigations of the esterolytic action of water soluble imidazole containing polymers. In our previous work we have explained increased reactivity of polymeric reactants in terms of electrostatic and cooperative effects. Recently, we have directed our efforts in emphasizing the apolar interaction as it has reflected dramatic rate enhancements and proven a predominant factor in determining the maximum catalytic efficiency. Polymeric catalysts which are included in this review are poly[l-alkyl-4(5)-vinyl-imidazoles] and their copolymers, hydro-phobic terpolymers of 4(5)-vinylimidazole, copoly[vinylamine/4(5)-vinylimidazole], and poly(ethylenimine-g L-histidine). All of these catalysts share the common property of water solubility and the capability of attaining high catalytic efficiencies which is attributed to apolar interactions. 

Isocyanide polymers functionalized with amino acid groups, typically di-or tripeptides containing histidine or serine, give enantioselective deacylation and rate enhancements. Their activity is increased by addition of cationic surfactants (Visser et al., 1985). 

Mn Peroxidase. The manganese peroxidase (MnP) is one of the two known enzymes capable of the oxidative degradation of lignin, an amorphous, random, aromatic polymer synthesized from p-hydroxycin-namyl alcohol, 4-hydroxy-3-methoxycinnamyl alcohol, and 3,5,-dime-thoxy-4-hydroxycinnamyl alcohol precursors by woody plants. Both enzymes contain the protoporphyrin IX heme prosthetic group, similar to the heme peroxidases with an L5-histidine and both use hydrogen peroxide as a substrate. However, the manganese peroxidase has an absolute requirement for Mn(II) to complete its catalytic cycle (50). The X-ray structure of this protein has recently appeared (51). 

Heme (7 a) containing l-(3-aminopropyl)imidazole (as proximal base) and also histidine (as distal base) was converted with polylaminomethylstyrene to get polymer porphyrin (2S) in a small degree of incorporation (<0.1%) l... 

Noguchi and Saito (31) have tested a number of compounds on NPA, including thermal copolymers containing histidine and glutamic acid or aspartic acid residues. Their method of preparing thermal polymers differed considerably from the usual procedures of Fox and co-workers. 

Another substrate hydrolyzed by thermal polyanhydroamino acids is p-nitrophenyl phosphate (NPP). Oshima 25) has tested acidic proteinoids, a histidine-rich proteinoid, and proteinoids that contain a relatively high proportion of basic and neutral amino acids (p. 377). These polymers were fractionated in water and aqueous alkali, and by molecular sieve chromatography. Soluble fractions were used in most experiments on catalysis. The possibility of microbial contamination was obviated indirectly by virtue of several circumstances. These included using fractions with molecular weights between 2500 and 4000, and adding toluene to the test reaction mixtures. The reactions were carried out at 30° in 0.03 M tris buffer, pH 7.6, in the presence of 1 pmole/ml of NPP and 0.03-1.5 mg/ml of thermal polymer pM ZnCU and IQfiM MgCl2 were also present in the solutions. Truly catalytic... 

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