| Over a century ago, as concepts of precise geometry receptors (“lock and key theory”) and specific targeting (“magic bullets”) were being evolved, the goal of pharmaceutical chemists was already, greater specificity. This three-part thesis is about therapeutic specificity and each portion addresses a different approach.; Therapeutic genomics—a specific gene as a target for a candidate therapeutic has become a hope of modern medicine. The aminomercaptotriazoles whose mechanism of inhibition of nitric oxide synthase is manifest at the gene level, are discussed in Section I covering Chapters 1–3.; Proteomics—a specific receptor or protein as a target for a candidate therapeutic—is exemplified by the mercurio-psoralens discussed in Section II covering Chapters 4 and 5. Here specificity is gained by a unique pendant -CH2-Hgx functionality, which binds to in vivo thiols as well as by a unique photo-activated chromophore, which requires light to anchor to its receptor.; Depot targeting or depot specificity is invoked when a polymer-drug conjugate is placed mechanically at a site of therapeutic opportunity. If properly designed and synthesized, specificity is achieved by chemical or enzymic hydrolysis of the active pharmaceutical from the polymeric backbone. In Section III, covering Chapters 6 and 7, we exemplify a hitherto unreported method of employing modified cellulose (and other polysaccharides) for controlled release of anticancer drugs.; Although each project reported herein is an independent entity, all share the overall goal of enhanced therapeutic specificity in small molecule pharmaceuticals. |
