Polymeric and Dendrimeric Vitamin B6 Mimics

The PEI-pyridoxamine polymer was treated with excess pyruvic acid in various buffer solutions, without added metal ions and with excess added EDTA. Kinetic studies revealed that the attached polymer increased the rate of pyridoxamine transamination with pyruvic acid by a factor of6700-8300 at pH 5.0. Under higher pH conditions, the rate enhancement decreased At pH 7.0 the rate enhancement by the polymer was still 2300 times, while at pH 8.0, the optimum for pyridoxamine itself, it was 1900. We also found that transamination by simple pyridoxamine showed strong metal ion catalysis - adding 1 equiv. of CuCl2 per pyridoxamine unit to the pH 5.0 solution increased the 

The rate enhancement of the polymer over that of simple pyridoxamine was a steep function of the length of the alkyl chains added, in polymers with roughly the same percentage of alkylation and of pyridoxamine attachment. At pH 7.0 and 30 °C, the acceleration over the rate with pyridoxamine was 160 for C-l chains, 180 for C-3, 500 for C-6, 1000 for C-9, 2300 for C-12, and 2500 for the C-15 and C-18 normal alkyl chains. This chain effect seems unlikely to involve hydrophobic binding of a substrate as hydrophilic as pyruvic acid. Instead the hydrophobic chains modify the pK,s of the amino groups in the polymer and also create a cavity in which the transamination can take place in a less than fully aqueous environment. 

To study the effect of polymer size on catalysis [37], pyridoxamine was linked to a series of PEIs with Mn = 600,1800,10 000, and 60 000, both simply permethylated and with additional attached dodecyl chains. The polymers were examined in the transamination of pyruvic acid and of phenylpyruvic acid, showing Michaelis-Menten behavior. The k2 and of i M determined showed only small variations with polymer size. Thus, the strong advantage of pyridoxamines attached to the Mn = 60 000 PEI, relative to simple pyridoxamine alone, was seen to almost the same extent with the smaller 

Notably, the PEI enzyme models do not have a well-defined structure, and each polymer molecule contains more than one coenzyme unit. To make more defined macro-molecular transaminase models we synthesized several water-soluble poly(amidoa- 

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