Surrogate substrate

The displacement of bound ligands by substrate. Jenkins pointed out that in many instances a substrate must displace another ligand from the active site to form the ES complex.40 For example, a binding site for an ionic substrate often already contains an ion, either of the product P or some other ion X which Jenkins calls a substrate surrogate. For this situation Eq. 9-14 must be replaced by the following set of equations ... 

Thus substrate surrogates at high concentrations are often competitive inhibitors. However, at low [X] the second term in Eq. 9-41 may be important and X then serves as an activator. Under many circumstances, Eq. 9-39 does not simplify further and a nonlinear relationship between 1/ v and 1 / [S] is observed, with the shape of the curves being influenced by the values of constants A and D (see also Section B,4)40... 

Structurally rigid substrate surrogates were added to the cubic section model before more flexible molecules as the following order signifies pentacyclic, tetracyclic, tricyclic, bicyclic ketones, trans/cis-decalones, methyl cyclohexanones and alkyl cyclohexanones. The hydroxyls of cyclohexanols were oriented axially with respect to cyclohexyl rings consistent with the Jones protocol and with the obsen/ation that... 

The priority number for an alcohol product was determined by the relative rate and the stereoselectivity of reduction. The priority number for each substrate surrogate was calculated from the rates of production of each enantiomeric alcohol product using the total relative rate of reduction vs cyclohexanol and the enantiomeric ratio (E) formula derived by Sih (Table 5). ... 

The X-ray crystallographic structure of the ternary complex, HLADH-NADH-dimethyl sulfoxide, DMSO, has been determined to 2.9 The crystallographic co-ordinates available from the Brookhaven protein data bank were entered into MACROMODEL and the amino acid residues surrounding the active site identified. Using MACROMODEL and ENZYME the substrate binding domain of HLADH was mapped as a cubic section model. The model obtained from this approach were compared with model col 3 obtained by substrate surrogate overlay. 

Model col 3 and the model constructed with all hydrogens in substrate surrogates (co13h) were compared with the cubic section model derived from display of the cubes occupied by residues of HLADH lining the substrate binding domain. Using... 

Comparison of the X-ray based cubic section model with the substrate surrogate derived cubic section model gave a view of the amino acid residues around the substrate binding domain (Figure 21). Forbidden and boundary regions defined by the substrate surrogate overlay method are near the side chains amino acid residues. Substrate interactions with surface of the amino acid residues could be estimated by molecular mechanics (MACROMODEL). 

Besides aUylsUanes or stannanes, allyl boron species have found widespread apphcations in synthesis. The Roush crotylation is a very well-estabhshed method with a broad substrate scope, and is therefore commonly used in organic synthesis [73]. The following example depicts a reversal in enantioselectivity induced by a cobalt complex present in the substrate. Roush et al. reported that the use of metal carbonyl complexes as substrate surrogates led to an improvement of enantioselectivity in the asymmetric crotylation of the respective aldehydes. These results were attributed to electronic effects exerted by the metal complexes that stabilize the transition state of the crotylation reaction (Scheme 3.47) [74]. 

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