Target-specific molecules

As mentioned earlier, penetration enhancers are extremely important for specific and rationally tailored delivery of pharmaceuticals. One novel class of such compounds are cell penetration enhancers (CPEs), which are unique peptides, first recognized in biological systems such as HIV, herpes enzymes, some fly [99] and frog species [100], and more [101]. These peptides have the ability to cause a perforation in the membranes of living cells thereby enhancing the penetration of molecules into the cells and target specific molecules to specific cells or nuclei [102, 103]. 

Brain capillary endothelial cells form the BBB. They are connected by extensive tight junctions and are polarized into luminal (blood-facing) and abluminal (brainfacing) plasma membrane domains (Hawkins et al., 2006). A pivotal function of the endothelial cells is to express transporters at the BBB and regulate the selective transport and metabolism of substances from blood to brain (Daneman et al., 2010). These transporters may be utilized to target specific molecules for delivery into the brain for therapeutic purposes. Figure 49.2 depicts various transport mechanisms for amino adds, glucose, proteins, and other molecules. 

The examples from the preceding discussion catalog the development of the field, which has largely led to increasing sophistication in the implementation of dipolar cycloadditions in target-specific molecule synthesis. The development of diastereoselective substrate-controlled methods as a general synthesis of chiral building blocks by use of nitrile-oxide dipolar cycloaddition reactions has only recently been heralded by the work of Kanemasa and Carreira. 

Other than directly targeting energy at specific molecules, hence reducing energy consumption, photochemical processes have several other green credentials ... 

Targeted contrast agents are specific and directed to a specific molecular or cellular target with an appropriate targeting ligand molecule. Recombinant high density lipoprotein (HDL)-like nanoparticles, a specific contrast agent for MRI of atherosclerotic plaques, has been reported [86] (Fig. 25). 

The technology of bioconjugation has affected every conceivable discipline in the life sciences. The application of a myriad of available chemical reactions and reagent systems for creating novel complexes with unique activities has made possible the assay of minute quantities of substances, the in vivo targeting of molecules, and the modulation of specific biological processes. Modified or conjugated molecules also have been used for purification, detection, or location of specific substances, and in the treatment of disease. 

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