Modeling Thiamine Catalysis in Protein and Peptide Systems

Modeling Thiamine Catalysis in Protein and Peptide Systems 

In a subsequent report, however, the thiazolopapains were shown to be competent in catalyzing a carbon-carbon bond-forming reaction of the acetoin condensation type (Fig. 14) [50]. The reaction of the papain derivatives with 6-oxo-heptanal was assayed at neutral pH (Fig. 14). The course of the reaction was monitored by HPLC and the products analyzed by H NMR. In the case of the 

Minor - Cyclization Fig. 14. Thiazolopapain-catalyzed reactions of 6-oxoheptanal 

3-benzylthiazolopapain, a near 4000-fold excess of substrate was almost entirely consumed (88 /o) within 150 h. 3-Methylthiazolopapain was much less efficient, converting only 28% of the substrate in the same time. The products generated included the expected cyclization product as a minor product (8 and 28% for 3-methyl- and 3-benzylthiazolopapain, respectively), and an unexpected condensation product as the major product (20 and 60%, respectively). In contrast, the simple thiazolium model compounds catalyzed the turnover of only 23% of the substrate in a comparable time period. Due to somewhat different reaction conditions, it is difficult to assess the extent of the influence of the papain active site but given the same amount of substrate, a 40-fold smaller amount of thiazolopapain was able to catalyze three times as many turnovers. 

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