Enantiomer binding

Linear Dichroism. The AA spectra of covalent adducts derived from the binding of racemic anti-BaPDE and of the enantiomer (+)-anti-BaPDE to DNA are positive in sign and similar in shape (5,31) this is expected since the (+) enantiomer binds more extensively to DNA than the (-) enantiomer (15). These covalent adducts are therefore of the site II type. 

Loukili, B. etal.. Study of tryptophan enantiomer binding to a teicoplanin-based stationary phase using the perturbation technique. Investigation of the role of sodium perchlorate in solute retention and enantioselectivity, J. Chromatogr. A, 986, 45,... 

If binding to the receptor involves the chiral centre, then we may see activity in only one enantiomer, but if binding does not involves the chiral centre, then there may be similar activities for each enantiomer. Binding close to the chiral centre may cause the same type of activity but of a different magnitude. A different pharmacological activity for each enantiomer almost certainly reflects different receptors. 

Using the crystal structures of two related RED enzymes of lignan biosynthesis, a provisional molecular model has been produced for the M. sativa IFR. A smaller binding pocket in the protein, in comparison to the other enzymes, is suggested to account for the specific enantiomer binding and processing of IFR. 

As mentioned earlier (Section 4.2.1.1), empirical rules for the enantioselectivity of hydrolases have been developed. It is important to keep in mind that these rules do not work for all substrates. Most rules are based on pockets, which indicate how the steric bulk of the substituents in the substrate fit into the environment of the active site. Thus, such rules have been suggested for pig liver esterase(PLE) [66], the protease subtilisin [66-68], and certain lipases [69-71]. For secondary alcohols, most lipases follow the simple rule of Kazlauskas, which was developed for Pseudomonas cepacia, and which is depicted in Figure 4.4 [72]. This model implies that the fast-reacting enantiomers binds to the active site as described in Figure 4.4, whereas the slowly reacting one is not able to achieve a comfortable fit, because it will require the large substituent L to fit into the smaller pocket. In contrast to lipases, subtilisin displays opposite enantioselectivity toward secondary alcohols [68]. 

The stereoselectivity for substrates bearing a small and a large substituent (e.g. a secondary alcohol as shown in fig.6) is explained by assuming that when the secondary alcohol is subjected to resolution by a lipase, the fast reacting enantiomer binds to the active side in the manner shown in fig. 6a, however, when the other enantiomer reacts with the lipase, it is forced to accommodate its large substituent into the smallest pocket (fig. 6b). This rule works well for secondary alcohols. However for primary alcohols, the rule is only applicable if an oxygen atom is attached to the stereocenter. A similar rue was also proposed for the resolution of carboxylic acids. 

Two-dimensional NMR has also been used to investigate the binding of the two enantiomers of the complex [Ru(phen)3]2+ (phen = 1,10-phenanthroline) to DNA using a decanucleotide as model and demonstrates that both enantiomers bind in the minor groove, rather than intercalatively (Eriksson et al., 1992). 

Chromatographic resolution of enantiomers. The enantiomers of the racemic compound form diastereomeric complexes with the chiral material on the column packing. One of the enantiomers binds more tightly than the other, so it moves more slowly through the column. 

The numerator in equation (22-26) represents the processes occurring in the mobile phase, while the denominator represents the processes occurring in the stationary phase. Such a situation can be realized by combining a chiral stationary phase in a push-pull mode with a chiral mobile phase of opposite con-hguration, where two enantiomers of the chiral selector are involved, one for the chiral stationary phase and the other for the chiral mobile phase. The most selective chiral chromatographic system should be encountered when one enantiomer binds to the immobilized chiral selector in the stationary phase, whereas the other enantiomer predominantly associates with the chiral mobile-phase additive [158]. The above treatment is applicable to all applications regarding the use of chiral mobile phases. 

Stereoselectivity in protein binding of enantiomers can also differ among species. For propranolol, a basic drug bound to AAG, the R-enantiomer binds less than the S-isomer in humans and dogs, and the reverse is observed in rat. Also, although the difference in binding is small in humans and dog, it is significant in rat. ... 

The mechanism of the Jacobsen HKR and ARO are analogous. There is a second order dependence on the catalyst and a cooperative bimetallic mechanism is most likely. Both epoxide enantiomers bind to the catalyst equally well so the enantioselectivity depends on the selective reaction of one of the epoxide complexes. The active species is the Co(lll)salen-OH complex, which is generated from a complex where L OH. The enantioselectivity is counterion dependent when L is only weakly nucleophilic, the resolution proceeds with very high levels of enantioselectivity. 

J ones,T. A. Structural basis for enantiomer binding and separation of a common b-blocker Crystal structure of cellobiohydrolase Cel7A with bound (S)-propranolol at 1.9.ANG. resolution,/. Mol. Biol., 2001, 305,79-93. 

A different situation is observed in the case of M. tuberculosis D-Ala forms the external aldimine, either, but also, slowly, the first quinonoid intermediate. It is claimed that this form reacts with pimeloyl-CoA to give d-AOP. However, the characteristics of the reference synthetic AOP are those of the racemic compound, as already discussed." Thus, this reaction with D-Ala should be reinvestigated. It was also reported that D-Ala inhibits the reaction with L-Ala however, the inhibition is no longer competitive, but of the linear mixed type, which would mean that the two enantiomers bind independently at different sites. 

Many of the chiral stationary phases have been developed by systematically applying the principle of reciprocity to the enantiomer binding interactions. A number of diverse racemates are analyzed on a chiral stationary phase containing as chiral selector the immobilized target molecule for the enantiomers of which a new selector is desired. The racemate showing the highest enantioselectivity in this system is selected, and... 

The metal complex Ru(phen) exists in two enantiomeric frums A and A both enantiomers bind DNA although their structural binding characteristics have remained unclear. Two-dimensional nmr expmments have demonstrated that both enantiomers bind to the minor groove of the AT region in the self-complementary duplex d(CGCGATCXjCG)]2. An octahedral ruthenium(II) complex (292) of the alkaloid 2-bromoleptoclinidinone has been prepared and... 

More reeently, Mesecar and Koshland [32], following an investigation of the enzyme isoeitrate dehydrogenase, have found that the three-point model does not always hold. Examination of metal-free crystals of the enzyme strueture reveals that only the 25,37 -(L)-isocitrate binds, whereas in the presenee of magnesium ions only the 22 ,3iS -(D)-enantiomer binds. Examination of x-ray structures of the two enzyme-substrate complexes reveals three common binding sites for both enantiomeric substrates that differ at a fourth site. Based on their observations, the authors proposed that the three-point model is only applicable if the assumption is made that the substrate can approach a planar surface from one direction. Thus a fourth location, either a direction requirement or an additional binding site, is essential to distinguish between a pair of enantiomers (Fig. 5). 

Shown is the configuration of (+)-carvone. (+)-Carvone is the principal component of caraway seed oil and is responsible for its characteristic odor. (—)-Carvone, its enantiomer, is the main component of spearmint oil and gives it its characteristic odor. The fact that the carvone enantiomers do not smell the same su ests that the receptor sites in the nose for these compounds are chiral, and that only the correct enantiomer binds well to its particular site (just as a hand requires a glove of the correct chirality for a proper fit). Give the correct (R) and (5) designations for (+)- and (—)-carvone. 

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