Transition state analogues methods

L. Pauling, Nature of forces between large molecules of biological interest, Nature 161, 707-709 (1948). a) V. L. Schramm, Enzymatic Transition State Analysis and Transition-State Analogues, Methods Enzymol. 308, 301-354 (1999) b) R. L. ScHOWEN, Transition States of Biochemical Processes, Plenum Press, New York (1978). 

Fig. 6.1. Summary of methods for selecting phage-displayed enzymes on die basis of catalytic activity (S substrate P product SS suicide substrate Bt biotin SV streptavidin TSA transition state analogue).

If the template was a transition state analogue for a particular enzyme reaction then the resulting polymer should contain myriads of sites capable to catalysing that reaction. So far this method has been used successfully to prepare catalysts for hydrolysis reactions [57] and Diels-Alder cyclizations [58] but it could equally easily be applied to mimic more traditional enzymes. 

Kobayashi S, Morii H, Itoh R, Kimura S, Ohmae M. Enzymatic polymerization to artificial hyaluronan a novel method to synthesize a glycosaminoglycan using a transition state analogue monomer. J. Am. Chem. Soc. 2001 123 11825-11826. 

Wolfenden R. Transition-state analogues as potential affinity labeling agents. Methods Enzymol 1977 46 15-28. 

The transformation of the cyano group could also introduce a new chiral center under diastereoselective control (Figure 5.13). Grignard-transimination-reduction sequences have been employed in a synthesis of heterocyclic analogues of ephedrine [81]. The preferential formation of erythro-/3-amino alcohols may be explained by preferential hydride attack on the less-hindered face of the intermediate imine [82], and hydrocyanation of the imine would also appear to proceed via the same type of transition state. In the case of a,/3-unsaturated systems, reduction- transimination-reduction may be followed by protection of the /3-amino alcohol to an oxazolidinone, ozonolysis with oxidative workup, and alkali hydrolysis to give a-hydroxy-/3-amino acids [83]. This method has been successfully employed in the synthesis L-threo-sphingosine [84]. 

R. Wischnat, R. Martin, C.-H. Wong, Synthesis of a New Class of N-Linked Lewis and LacNAc Analogues as Potential Inhibitors of Human Fucosyltransferases A General Method for the Incorporation of an Iminocyclitol as a Transition-State Mimetic of the Donor Sugar to the Acceptor , J. Org. Chem 1997, 63, 8361-8365. 

Selected entries from Methods in Enzymology [vol, page(s)] Acetylthiocholine as substrate, 251, 101-102 assay by ESR, 251, 102-105 inhibitors, 251, 103 modification by symmetrical disulfide radical, 251, 100 thioester substrate, 248, 16 transition state and multisubstrate analogues, 249, 305 enzyme receptor, similarity to collagen, 245, 3. 

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