Lead, preferential binding

The binding sites of platinum to DNA and its separate bases are expected to be similar to those for the other -metals, provided that the platinum binds through one site only. However both PtClf- and such molecules as Pt(NH3)2Cl2, cis- and trans-iorms, can act bifunctionally. Indeed preferential binding is expected to yield chelated complexes of one type or another. For example the cis-chelation will lead to the following complexes. 

One study (DeLeo et al., 1988 Fowler et al., 1989) has found that neutral H at the B site in Si has a tendency to preferentially bind to one of the two Si neighbors, leading to an asymmetric configuration, with Si—H distances of 1.48 A and 1.77 A respectively. This tendency was interpreted in terms of a pseudo-Jahn-Teller distortion. However, the potential barrier that leads to the asymmetric position is so low (< 0.2 eV) that it can readily be surmounted by zero-point motion of the proton. Experimental observation of such an asymmetry is therefore unlikely, except maybe through an isotope shift measurement in an infrared experiment (DeLeo et al., 1988). None of the other theoretical approaches has produced this type of asymmetry. 

Currently available BAS include cholestyramine, colestipol and colesevelam hydrochloride (colestimide). Cholestyramine comprises a long-chain polymer of styrene with divinylbenzene trimethylbenzylammonium groups, whereas colestipol is a long-chain polymer of l-chloro-2,3-epoxypropane with diethylenetriamine. Colesevelam HCl is poly(allylamine hydrochloride) cross-linked with epichlorohydrin and alkylated with 1-bromodecane and 6-bromo-hexyl-trimethylammonium bromide. Bile-acid binding is enhanced and stabilised in the latter compound by long hydrophobic sidechains, increased density of primary amines, and quaternary amine sidechains. For this reason, colesevelam HCl exhibits increased affinity, specificity and capacity to bind bile acids compared with the other BAS. Colesevelam HCl also binds dihydroxy and trihydroxy bile acids with equal affinity, contrasting with cholestyramine and colestipol that preferentially bind dihydroxy bile acids (CDCA and deoxycholic acid). The latter BAS can lead to an imbalance towards trihydroxy bile acids and a more hydrophilic bile-acid pool. 

Based on the observation that ellipticine binds preferentially to the RNAiDNA hybrid poly rArpoly dT, an assay was developed to rapidly screen large numbers of potential lead compounds for this property <2001JA6742>. The 3D structures of the compounds that preferentially bind to the RNAiDNA hybrid (ellipticine, ethidium, coralyne. 

Fig. 26 A Chiral memory effect applied to the construction of a chiral softball homo-dimeric capsule made of achiral units. B Racemic softball binds a chiral guest leading preferentially to one diastereoisomer. Fast exchange, compared to capsule s racemization rate, with a better achiral guest allows preparation of enantioenriched capsule...

This would lead us to expect selectivity for copper over zinc as observed as well as preferential binding to copper over nickel. It must be noted that the symmetrical patellamide A is non-selective for Cu, even though the Irving-Williams series would... 

Addition of Mg to these complexes leads to their dissociation. However, addition of alkali leads to the appearance of cleaved DNA molecules having protein covalently attached to the DNA (see below). This enzyme also forms complexes with relaxed duplex DNA but these complexes are not dissociated by the addition of Mg and cleavage of the DNA is not found when alkali is added (Liu and Wang, 1979). Complexes between procaryotic topoisomerase I and DNA can also be detected by their retention on nitrocellulose filters. Using this method the preferential binding of the enzyme to an internal single-strand break in a linear duplex DNA has been shown (Dean et al., 1982 Dean and Cozzarelli, 1985). 

A model for MerR metalloregulation. In the absence of MerR, RNA polymerase binds and transcribes the MerR promoter. In the presence of MerR, the preferential binding of MerR to the promoter is observed that inhibits transcription by the polymerase. The addition of Hg + then leads to a conformational change that promotes binding of the polymerase, substantially increasing transcription. Reproduced with permission from Reference 90a. 

Busch classified templates as thermodynamic [13a, 27] or kinetic [ 13b, 28], A thermodynamic template shifts the position of equilibrium of a reversible reaction by preferentially binding one product. Kinetic templates operate on irreversible reactions by stabilizing the main transition states leading to the desired product. Kinetic templates almost invariably bind the product more strongly than the starting material, so they also favor the formation of the product thermodynamically. Conversely, thermodynamic templates are likely to accelerate formation of the product by transition state stabilization, so classification of the observed effect depends crucially on the reaction conditions and time scale. 

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