Amino acid ester transport

Han, H.-K., D.-M. Oh, and G. L. Amidon. Cellular uptake mechanism of amino acid ester prodrugs in Caco-2/hPEPTl cells overexpressing a human peptide transporter. Pharm. 

Han, H., et al. 5 -Amino acid esters of antiviral nucleosides, acyclovir, and AZT are absorbed by the intestinal PEPT1 peptide transporter. Pharm. 

Sawada, K., et al. Recognition of L-amino acid ester compounds by rat peptide transporters PEPT1 and PEPT2. J. Pharmacol. Exp. Ther. 1999, 291, 705-709. 

X. Song, P. L. Lorenzi, C. P. Landowski, B. S. Vig, J. M. Hilfinger, and G. L. Amidon. Amino acid ester prodrugs of the anticancer agent gemcitabine synthesis, bioconversion, metabolic bioevasion, and hPEPTl-mediated transport. Mol Pharm 2 157-167 (2005). 

A number of workers have observed amino acids in lipide extracts, including those of microbial origin (11, 12, 17, 29). Recently, Macfar-lane (34) has reported that most of the phospholipide in Clostridium welchii is bound to amino acids and that some of this material occurs as the O-amino acid ester of phosphatidylglycerol. The relatively prominent occurrence of lipides in cell membranes has led to the recurrent suggestion that transport of hydrophilic substances through such membranes would be greatly facilitated by combination with hydrophobic substances. Consequently, most workers who have observed the incorporation of amino acids into lipide fractions quite naturally... 

These examples are unusual in that vaiacyciovir is an amino acid ester of a nucleoside that does not closely resemble the normal dipeptide substrates of the PEPT-1 transporter. A number of other drugs (such as methotrexate) are probably transported by proteins that normally transport the metabolites that they resemble and antagonize (e.g., folates). However, these cases represent fortuitous examples of drug transportability Tiatural selection" during the drug discovery and development process. With increased understanding of the specificity determinants of... 

Umapathy, N.S., Ganapathy, V. and Ganapathy, M.E. (2004) Transport of amino acid esters and the amino-acid-based prodrug valganciclovir by the amino acid transporter ATB(0, +). Pharmaceutical Research, 21 (7), 1303-1310. 

Miyake, H., Yamashita, T., Kojima, Y., Tsukube, H. (1995). Enantioselective transport of amino acid ester salts by macrocyclic pseudopeptides containing N,N -ethylene-bridged-dipeptide units. Tetrahedron Lett., 36, 7669-72. 

As a result, there are a number of reports on the extraction and membrane transport of amino acids from acidic media. Particularly numerous are the data on amino acid esters, as they are more hydrophobic and exist as cations in a wider pH range. All the classes of hosts listed in the preceding section were used. Stochastic selection includes work on crowns and aza crowns [143—148], calixarenes [100], podands and natural ionophores [149,150] in fact, most of the papers mentioned above on enantiodiscrimi-nation deal with amino acid esters for evident reasons. 

Chromatographic batch reactors are employed to prepare instable reagents on the laboratory scale (Coca et al., 1993) and for the production of fine chemicals. These applications include the racemic resolution of amino acid esters (Kalbe, Hbcker, and Berndt, 1989), acid-catalyzed sucrose inversion (Lauer, 1980) and production of dextran (Zafar and Barker, 1988). Sardin, Schweich, and Viller-maux (1993) employed batch chromatographic reactors for different esterification reactions such as the esterification of acetic acid with ethanol and the transesterification of methylacetate. Falk and Seidel-Morgenstern (2002) have investigated the hydrolysis of methyl formate. Strohlein et al. (2006) measured the esterification of acrylic acid with methanol and validated the transport dispersive model for process simulation. 

Chang, S.K. Hwang, H.S. Son, H. Youk, J. Kang, Y.S. Selective transport of amino acid esters through a chloroform liquid membrane by a calix[6]arene-based ester carrier. J. Chcm. Soc., Chem. Commun. 1991, 217. 

Mutihac, L. Buschmann, H. Tudorescu, A. Mutihac, R. Some aspects of extractability and transport of amino acid esters by calixarenes. J. Inclusion Phenom. Macrocycl. Chem. 2003, 47, 123-128. 

Toad bufadienolides occur not only by themselves but also in a conjugated form, sulfates, dicarboxylic esters and amino acid-dicarboxylic acid esters have all been reported (Steyn and van Heerden 1998). Because of the activity of the bufadienolides in inhibiting active monovalent cation transporters, it is suggested that these compounds have a role in maintaining sodium homeostasis in toads that migrate between fresh and salt water environments (Flier, I idwards, Daly and Myers 1980). 

---