Drugs, site directed

As noted above, the steroid nucleus has been a favorite for the design for site directed alkylating antitumor drugs. Thus reaction of prednisolone (62) with anhydride 63 affords the 21 acylated derivative, prednimustine (64). ... 

Common to all three aims is that silico-derived predictions can rationalize experimental efforts either by well-directed very specific molecular biological experiments like site directed mutations or e.g., by reducing the number of compounds to screen experimentally for drug design. 

Hurwitz, E., Kashi, R., Burowsky, D., Arnon, R., and Haimovich, J. (1983b) Site-directed chemotherapy with a drug bound to antiidiotypic antibody to a lymphoma cell-surface IgM. Int. J. Cancer 31, 745. 

H. J. Bohm, Site directed structure generation by fragment joining, Perspect. Drug Disc. 

Tapia, O., Paulino, M. and Stamato, F. M. L. G. Computer assisted simulations and molecular graphics methods in molecular design. 1.Theory and applications to enzyme active-site directed drug design,... 

As mentioned in Section 11.2, a special class of proteinaceous targeting constructs are those in which a therapeutic protein is used as the active drug substance. In such a preparation, the protein is redirected to the target tissue by the attachment of site-directing ligands such as those discussed in Section 11.3. For instance, interferon beta (IFN- 3) can be redirected to the liver by enz5matic desialylation in a procedure similar to that described earlier for fetuin (Section 11.3.1). The resultant asialo-IFN- 3 was found to have an in vivo anti-viral effect when tested in a hepatitis B model in athymic nude mice [54]. 

Resistance of pathogenic microorganisms to beta-lactam antibiotics can result from one or a few of the mechanisms listed below inability of the drug to directly find an active site a change in PBP function, which is expressed in the reduction of affinity to the drag or inactivation of the drug by bacterial enzymes. 

Fig. 3. Possible interactions between PKC and MDRl-mediated drug resistance. Activation of PKC might activate the drug efflux by phosphorylation of PGP (A), induce or activate proteins which modulate PGP (B, Castro et al., 1999), or induce the transcription and translation of MDRl-mRNA (C). Inhibitors of PKC might prevent phosphorylation of PGP leading to a decrease the drug efflux (D). inhibit the efflux of drugs by direct interaction with the drug binding site(s) or the ATP-binding sites of PGP (E), or prevent the expression of MDRl-mRNA (F)...

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