Unreactive structural analogues

Interestingly, a host of organic reactions are usually involved, having different specific experimental parameters, that do not eventually ensure reaction selectivity and under such critical situation(s) certain functional moieties need to be protected by first converting them into unreactive-structural-analogues . Hence, the protection of functional moieties may be accomplished by the help of a plethora of known organic reactions. 

The physiological reaction catalyzed by OYE has been a long-standing mystery. OYE is often assayed as an NADPH oxidase. However, its reaction with molecular oxygen is quite slow for an oxidase (10 —lO mol 1 s ), casting doubt on the relevance of O2 as a substrate. Curiously, both a- and /3-NADPH rapidly reduce OYE, with the unnatural ct-isomer being a better substrate. The crystal structure of OYE complexed with an unreactive NADPH analogue shows that C4 of the nicotinamide moiety lies over N5 of the flavin, as required... 

Fig. 87.10 Structures of ( -selective prenyltransferases (1X06). (a) Homodimeric structure of E. coli UPP synthase, (b) monomer in complex with and an unreactive FPP analogue, and (c)...

The structure of the reactive ternary complex composed of the enzyme NAD+, and 4-bromobenzyl alcohol was solved at 2.9-A resolution.14 This was possible because there is a favorable equilibrium between this complex and the enzyme-bound ternary complex reaction product of NADH and 4-bromo-benzaldehyde. The structure of the unreactive product-like complex composed of the enzyme, the coenzyme analogue H2NADH (i.e., NAD+ in which the nicotinamide ring has been reduced to 1,4,5,6-tetrahydronicotinamide), and trans-4- (N, A-dimethylamino)-cinnamaldehyde (DACA) was also solved at the same resolution.18... 

The first attempts to determine the structure of a productively bound enzyme-substrate complex were based on extrapolation from the structures of stable enzyme-inhibitor complexes. (The classic example of this, lysozyme, is discussed in section F3.) Such extrapolation may be done in several ways. For example, a portion of the substrate may be bound to the enzyme and the structure of the remainder determined by model building. An alternative method is to use a substrate analogue that is unreactive because its reactive bond is modified. Typical examples are the binding of phosphoglycolohydroxamate, a substrate analogue, to triosephosphate isomerase,44 or a piece of DNA, which lacks the reactive 2 -OH groups, to a ribonuclease.45... 

The homoleptic sterically hindered thiolate complex [Mo2(TMT)g] containing Mo— Mo triple bonds was first prepared by a multistep reaction (35). The X-ray crystal structure showed a staggered configuration for the thiolate ligands with an Mo— Mo distance of 2.228(1) A (35). They were synthesized subsequently by a simple one-step synthesis involving the reaction of M0CI4 with the TIPT anion in 1,2-dimeth-oxyethane and structurally characterized. A study of their chemistry showed them to be rather unreactive compared with their alkoxide analogues (36). 

Essential characteristics of synthetic enzyme analogues are summarized in the Box on page 460. Many of these features are closely interrelated, such as complexation, saturation kinetics, and substrate selectivity, as well as competitive inhibition by stronger binding substrates, which are less reactive or completely unreactive. Regio- or stereoselectivity, if applicable, can change in comparison to the uncatalyzed process by a variation in structure or by disposition of the transition state, for example, from early to late or from an SN1 to an Sn2 mechanism. 

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