Glycoprotein transport molecules

The Admensa Interactive tool developed by scientists from Inpharmatica incorporates several ADME properties, namely log P, log Dy 4 (log P at pH 7.4), aqueous solubility, human intestinal absorption, BBB penetration, cytochrome P450 (CYP) affinities, P-glycoprotein transport, hERG inhibition and PPB to score and prioritize their molecules. 

Figure 9.3. Resulting pharmacophore for P-glycoprotein actively transported molecules. The depicted molecule is the analgesic (narcotic) sufentanyl. The colored areas around the molecules are the GRID fields produced by the molecule yellow for DRY probe, green for TIP probe and blue for N1 probe.

The thyroid gland extracts iodine from the circulation and contains up to 90% of the total body iodine. The accumulation of iodine from the bloodstream to thyroid foUicles is mediated by a transmembrane transporter molecule called the sodium iodide symporter (NIS) (Dai et al., 1996). It is a membrane-bound glycoprotein with 13 transmembrane domains and is expressed on the basolateral membrane of thyroid follicular cells. 

D. and their esters are present in practically all membranes of eukaryotic cells (except those of mitochondria and plastids) and function in the biosynthesis of glycoproteins and glycolipids as carriers of and transport molecules for oligosaccharides. D. are also com-... 

There is considerable evidence that a second trans-poson in the ER membrane is involved in retrograde transport of various molecules from the ER lumen to the cytosol. These molecules include unfolded or mis-folded glycoproteins, glycopeptides, and oligosaccharides. Some at least of these molecules are degraded in proteasomes. Thus, there is two-way traffic across the ER membrane. 

Fig. 4.6(a) Migration of LHRH neurocrine cells prenatal transportation along the track of extra-bulbar VN axons (caudal branch). CB, cribriform plate FB, forebrain cell types, TAG-1, transient axonal surface glycoprotein and N-CAM, neural cell adhesion molecule (from Yoshida et al, 1995). 

In a study of p-glycoprotein substrates vs. non-substrates, Varma et al. [48] concluded that substrate molecules with high passive permeability overwhelmed the transporter while substrate molecules with moderate passive permeability were more affected by p-glycoprotein. Approximately half of 63 p-glycoprotein substrates studied had MW >400 and PSA > 75 indicating that larger, more polar molecules are more likely to be p-glycoprotein substrates. 

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