Dual binding mechanism

Recently, Horvath and co-workers (B9, N1) introduced the concept of a dual binding mechanism to explain the atypical behavior of some solutes under reversed-phase conditions. In addition to solvophobic forces, it is possible for solutes to interact with the free surface silanols of the silica-based hydrocarbonaceous packing material. The term silanophilic interaction has been introduced to denote a reversible binding mechanism between solute molecules and silanol groups. 

This dual binding mechanism satisfactorily explains the anomalous retention of many solutes when viewed in purely solvophobic terms and will no doubt lead to the explanation of other solutes. 

Heparin binds both to thrombin and AT at the same time and the basis of its action is this dual binding mechanism. The portion of heparin binding to thrombin is 5-6 residues in length and the interactions with the protein are similar to those shown for AT. It has been shown that the minimum length of sulphated polysaccharide requited for binding to both AT and thrombin, and thus for thrombin inhibition, is seventeen residues. 

Anti-transferrin receptor/anti-DT bispecific antibodies were used to deliver CRM107 into cells via the transferrin pathway and to demonstrate that the acid-release mechanism was functioning properly. This receptor was targeted because it normally cycles protein-bound iron through acidic endosomes where the Fe3+ is released by the low pH (26). The dual binding capacity of the bispecific antibodies was confirmed by their ability to specifically deliver [125I]-diphtheria toxin to transferrin receptors present on intact human cells. 

Elucidating the function of distal Cub in O2 reduction by HCOs has recently been the major focus of biomimetic studies of HCOs ". Cub has long been assumed to facilitate 0-0 bond heterolysis, or stabilize peroxo-level intermediates against dissociation, by forming a bridged Feaj-ZO j-Cug unit upon O2 binding Such a situation would imply that a bimetallic catalytic site is required for efficient O2 reduction. This would be comparable to the dual site mechanism of O2 reduction at Pt , which is supported by some recent results . However, no peroxo-level intermediates of any kind have ever been observed during O2 reduction by HCOs and it remains uncertain whether an intermediate where... 

The empirical observation that (—)-sparteine 55 is necessary for catalysis implicates a base-promoted pathway in the mechanism. In the first step, a palladium alk-oxide is formed after alcohol binding, followed by p-hydride elimination of the alkoxide to yield a ketone product. On the basis of a kinetic study of the enantio-selective oxidation of 1-phenylethanol, it was revealed that (—)-sparteine plays a dual role in the oxidative kinetic resolution of alcohols, as a ligand on palladium and an exogeneous base " ... 

Enkephalins could be implicated in dopamine mesoaccumbens-depen-dent appetitive motivation and behavioral positive reinforcement by separated mechanisms involving both mu and delta receptors. Activation of the former in heroin abusers produces sedation and overstimulation, lack of vigilance, and possibly fear. These effects cannot be reached with dual inhibitors, and one can speculate that this is related to an increased level of endogenous enkephalins leading to a preferential interaction with delta receptors for both binding and anatomical reasons. 

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