Nucleic acids pharmacological activity

Targeting of therapeutics, whether they are chemical entities, peptides, proteins or nucleic acid polymeric substances, relies on the release of the drug from the carrier and subsequent access to the molecular target. Advances in the understanding of membrane structure, functions and properties of the various cellular organelles is the basis for directing the pharmacologically active components to the correct cellular compartments [39]. 

Pharmacology Inhibits the replication of influenza A virus isolates from each of the subtypes. Amantadine s antiviral activity is not completely understood. Its mode of action appears to be the prevention of the release of infectious viral nucleic acid P.1044... 

Peptides—Congresses. 3. Nucleic acids—Congresses. 4. Structure-activity relationship (Pharmacology)— Congresses. 5. Stereochemistry—Congresses. 

The pharmacology of these drugs, which are also used in the treatment of malaria, is presented on p. 351. The mechanism of their anti-inflammatory activity is uncertain. Besides inhibiting nucleic acid synthesis, they are known to stabilize lysosomal membranes and trap free radicals. In treating inflammatory disorders, they are reserved for rheumatoid arthritis that has been unresponsive to the NSAIDs or else they are used in conjunction with an NSAID, which allows a lower dose of chloroquine or hydroxychloroquine to be administered. These drugs have been shown to slow progression of erosive bone lesions and may induce remission. They do cause serious adverse effects (see p. 351). 

Nucleoside reverse transcriptase inhibitors (NRTIs) were the first class of medications approved for the management of HIV infection. They are structural analogues of nucleic acids. They undergo intracellular phosphorylation to a triphosphate metabolite and it is this metabolite that is pharmacologically active against reverse transcriptase. Drugs in this class include abacavir, adefovir, didanosine, emtricitabine, lamivudine, stavudine, tenofovir, and zidovudine. 

Nucleosides can be structurally modified to generate pharmacologically active derivatives that, by retaining most of the metabolic properties of the parent compounds, can be transported into the cell and metabolized. They can then interfere with nucleic acid synthesis, thus promoting either antiproliferative effects or resistance to virus replication in infected cells. This is the rationale for using nucleoside derivatives in cancer and AIDS therapies. 

What makes the thiated nucleobases so markedly different from the normal ones Put in the other words, what is a key effect of the thio substitution which, in turn, causes a variety of bizarre effects in the interaction of thiouracils with water, in proton migration, recognition patterns, biological and pharmacological activities, etc., etc. There are actually two key effects underlying the thio substitution and certainly inter-related. One is that such substitution dramatically changes the structural features of nucleic acids whereas the other is due to the drastic change of their functional ones expressed in terms of intermolecular interactions. 

---