Receptor activity, conjugates

Fig. 2 Multifunctional polymeric micelles composed of a block copolymer of poly(ethylene glycol) and polyaspartate with tumor selectivity for active drug targeting and pH sensitivity for intracellular site-specific drug transport. Folic acid with high tumor affinity due to the overexpression of its receptors was conjugated onto the surface of the micelle (adapted from Ref. [114] with permission)...

Feng, X, Zhang, J, Barak, LS, Meyer, T, Caron, MG and Hannun, YA (1998) Visuahzation of dynamic trafficking of a protein kinase C betall/green fluorescent protein conjugate reveals differences in G protein-coupled receptor activation and desensitization. Journal of Biological Chemistry, 273, 10755-10762. 

Fenoldopam (76) is an antihypertensive renal vasodilator apparently operating through the dopamine system. It is conceptually similar to trepipam. Fenoldopam is superior to dopamine itself because of its oral activity and selectivity for dopamine D-1 receptors (D-2 receptors are as.sociated with emesis). It is synthesized by reduction of 3,4-dimethoxyphenylacetonitrile (70) to dimethoxyphenethylamine (71). Attack of diis last on 4-methoxystyrene oxide (72) leads to the product of attack on the epoxide on the less hindered side (73). Ring closure with strong acid leads to substituted benzazepine 74. O-Dealkylation is accomplished with boron tribromide and the catechol moiety is oxidized to the ortho-quinone 75. Treatment with 9NHC1 results in conjugate (1,6) chloride addition and the formation of fenoldopam (76) [20,21]. 

Intracellular single-chain mAbs are supposed to prevent membrane localization of the receptors. Antireceptor mAbs conjugated to radionucleides, or to prodrugs, are tested as well, and DNA vaccines may induce an active immune response against RTK overexpressing tumors. 

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