Enzyme mimics.
'Two is better than one' in cooperating systems. Synthetic ditopic host molecules have been constructed from cyclodextrins and from synthetic hydrophobic cavities bridged with simple connectors or with catalytic groups. These host molecules show very strong binding of appropriate substrates, and selective catalysis. A cyclodextrin bis-imidazole shows bifunctional catalysis of the cleavage of a cyclic phosphate that is simultaneous, judged from isotopic studies. The best geometry is consistent with mechanistic evidence on the preferred mechanism for such bifunctional catalysis. Certain polar compounds bind to a still unidentified cellular receptor and induce differentiation of malignant cells. Ditopic drugs that have been designed and synthesized bind strongly to two receptor sites and induce cancer cell differentiation at low concentrations with few side-effects. Clinical results with these compounds are already promising in a few cancer patients.
Department of Chemistry, Columbia University, New York, NY 10027.
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Breslow
D000818:Animals; D000970:Antineoplastic Agents; D002384:Catalysis; D002454:Cell Differentiation / Q000187:drug effects; D003505:Cyclodextrins / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D004798:Enzymes / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism
D000970:Antineoplastic Agents; D003505:Cyclodextrins; D004798:Enzymes; D010710:Phosphates