Receptor targeting

Care should be exercised when attempting to interpret in vivo pharmacological data in terms of specific chemical—biological interactions for a series of asymmetric compounds, particularly when this interaction is the only parameter considered in the analysis (10). It is important to recognize that the observed difference in activity between optical antipodes is not simply a result of the association of the compound with an enzyme or receptor target. Enantiomers differ in absorption rates across membranes, especially where active transport mechanisms are involved (11). They bind with different affinities to plasma proteins (12) and undergo alternative metaboHc and detoxification processes (13). This ultimately leads to one enantiomer being more available to produce a therapeutic effect. 

In this part we shall examine the potential of NT receptors-targeting agents as therapeutic drugs. 

Somatostatin Receptor Scintigraphy and Receptor-Targeted Radiotherapy... 

Richter M, Zhang H (2005) Receptor-targeted cancer therapy. DNA Cell Biol 24 271-282... 

A large number of other non-paralytic but biologically active peptides have been purified and sequenced. In most cases however, the detailed mechanism of action has not yet been elucidated. Clearly, Conus venoms will be a rich source of such peptides that can be used to probe various receptor targets, particularly in the central nervous system. 

Boulanger, A., P. McLemore et al. (2003). Identification of beta-carotene 15,15 -monooxygenase as a peroxisome proliferator-activated receptor target gene. FASEB J. 17(10) 1304—1306. 

Hazard identification consists in identifying the type and nature of adverse effects caused by the agent in the receptor (target organism, system, or (sub) population). 

Licha K, Hessenius C, Becker A, Henklein P, Bauer M, Wisniewski S, Wiedenmann B, Semmler W (2001) Synthesis, characterization, and biological properties of cyanine-labeled somatostatin analogues as receptor-targeted fluorescent probes. Bioconjugate Chem 12 44—50... 

Excellent reviews have been written on the topic of chelating agents, radiolabeling, and receptor targeting. Because this research area, by definition, is a multi-disciplinary area, these topics are usually treated to some degree in any of these review articles.33-36... 

Various researchers have applied the receptor-targeted strategy in pharmacological models for tumor-targeted delivery of pDNA expressing tumor necrosis factor alpha (TNFa). For example, Tf- or Tf-PEG-shielded PEI polyplexes have been used... 

Shir A, Ogris M, Wagner E, Levitzki A (2006) EGF receptor-targeted synthetic double-stranded RNA eliminates glioblastoma, breast cancer, and adenocarcinoma tumors in mice. PLoS Med 3 e6... 

Ziady AG, Ferkol T, Dawson DV, Perlmutter DH, Davis PB (1999) Chain length of the polylysine in receptor-targeted gene transfer complexes affects duration of reporter gene expression both in vitro and in vivo. J Biol Chem 274 4908 1916... 

Shukla, S., Wu, G., Chatterjee, M., Yang, W., Sekido, M., Diop, L.A., Muller, R., Sudimack, J.J., Lee, R.J., Barth, R.F., and Tjarks, W. (2003) Synthesis and biological evaluation of folate receptor-targeted boro-nated PAMAM dendrimers as potential agents for neutron capture therapy. Bioconjugate Chem. 14, 158-167. 

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