Transition state analogue substrate

Kobayashi, S., Kiyosada, T., Shoda, S.-L Synthesis of artificial chitin irreversible catalytic behavior of a glycosyl hydrolase through a transition state analogue substrate. J. Am. Chem. Soc. 118, 13113-13114 (1996)... 

Transition-state analogue substrate Trimer of trimethylene carbonate 11-Undecanolide Ultrahigh molecular weight... 

It has been found that various sugar oxazoline derivatives serve as monomers for enzymatic catalysis to produce natural and unnatural mucopolysaccharides, in which the monomers were designed and synthesized on the basis of the transition-state analogue substrate (TSAS) concept vide infra).All the sugar oxazoline monomers are of AB-type structure mentioned in Section 4.15.3.2. 

Nebularine. Nebularine(44) is a naturaHy occurring purine riboside isolated from S.jokosukanensis (1,3,4). It is phosphorylated, and inhibits purine biosynthesis and RNA synthesis, but is not incorporated into RNA by E. coli RNA polymerase. It has also found appHcation as a transition state analogue for treatment of schistosomiasis and as a substrate for the restriction endonuclease, Hindll (138—141). 

Amide hydrolysis at alkaline pH involves a tetrahedral anionic intermediate, which was mimicked by the transition state analogue [49], an /V-aryl arylphosphonamidate, appropriately related to substrate anilide [50] (Fig. 18) (Appendix entry 2.8). 

The enzyme carboxypeptidase A is particularly amenable to structural investigation crystal structures of the enzyme, of complexes of the enzyme with substrates, substrate analogues and inhibitors, and of transition-state analogues are available. To isolate an enzyme-substrate complex for a one-substrate enzyme reaction, or for an enzyme reaction where water is a... 

Many of the 60 known reactions catalyzed by monoclonal antibodies involve kinetically favored reactions e.g., ester hydrolysis), but abzymes can also speed up kinetically disfavored reactions. Stewart and Benkovic apphed transition-state theory to analyze the scope and limitations of antibody catalysis quantitatively. They found the observed rate accelerations can be predicted from the ratio of equilibrium binding constants of the reaction substrate and the transition-state analogue used to raise the antibody. This approach permitted them to rationalize product selectivity displayed in antibody catalysis of disfavored reactions, to predict the degree of rate acceleration that catalytic antibodies may ultimately afford, and to highlight some differences between the way that they and enzymes catalyze reactions. 

---