Polyvalent interactions

M. Mammen, S.-K. Choi, and G. M. Whitesides, Polyvalent interactions in biological systems Implications for design and use of multivalent ligands and inhibitors, Angew. Chem. Int. Ed. Engl., 37 (1998) 2754—2794. 

Analysis by XPS after incorporation of the linear or dendritic cationic polymers showed an increase in the atom % N consistent with incorporation of an N-rich polycation. The polyvalent interactions between the cationic polyelectrolytes and the poly(sodium acrylate)graftson PE were stable to Soxhlet extraction with 95% ethanol, repeated acid/base treatment, and soaking or sonication in isopropanol and THE However, in these cases, simple acid treatment did not release the cationic polymer as was the case with PAA/Au grafts even though grafting in both cases was reportedly ionic and not covalent. 

Thus, our work suggests that, although other more complicated methods have also been put forward, the prediction that polyvalent interactions should be equal to monovalent interactions raised to the A th power, where N is the number of receptor-ligand interactions, is experimentally valid. Our mannose-/glucose-fiinctionalized dendrimer results suggest that the affinity of multivalent associations can be attenuated in predictable, reliable ways based on the monovalent affinities of the ligands (Wolfenden and Cloninger 2005, 2006). 

Some of the best understood polyvalent interactions are found in immune and host defense systems as well as ligand-receptor activation. An example is the use of a polyvalent immunogen based on a synthetic peptide to elicit immune responses. The subsequent production of site-specific antibodies can then be employed to confirm the identity of proteins derived from recombinant DNA, to explore biosynthetic pathways, to define precursor-product relationships (e.g., proenzyme and preproenzyme), and to determine protein structural domains.19 ... 

Self-assembly of such dendrimers is a dynamic equilibrium process (Fig. 8.9). Conceivably, the non-covalent polyvalent ligands can be optimised with regard to their size and shape in the presence of natural multivalent receptors, as a kind of template for their own multivalent inhibitor, and thus open up a range of physiologically relevant polyvalent interactions [40 a]. 

The construction of neoglycoconjugates has reached an unprecedented level of sophistication and imagination. This is undoubtedly the result of increased interest from the traditional glycobiology community as well as by a wide range of synthetic chemists now entering the field, a trend facilitated by access to modem analytical tools. The degree of refinement in the techniques employed to quantitate polyvalent interactions has also steadily increased over the last few years (reviewed in Ref. 92). 

From a medicinal chemistry point of view, carbohydrates are an uninteresting class of molecules for drug development because they are too difficult to synthesize on a large scale and too hydrophilic to have good bioavailability, and they are generally orally inactive and unstable. Perhaps the most fundamental problem is that carbohydrates bind their receptors or enzymes with weak affinity, usually with dissociation constants in the millimolar range. Polyvalent interactions are, however,... 

Polyvalent Interactions in Biological Systems Implications for Design and Use of Multivalent Ligands and Inhibitors. Ange-wandte Chemie International Edition, 2754-2794. 

Multi- and polyvalent interactions between lectins and glycans are of fundamental importance for the interaction of biological surfaces. Lectins are proteins with defined glycan-recognition domains on the surface of viruses and bacteria as well as of plant and animal cells. Affine inhibitors of lectins are, therefore, suitable for clarifying the function of defined carbohydrate stmctures, when they are used as a competitive binding partner. They also provide an opportunity for pharmacological intervention. The phenomenon of... 

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