Tethered prodrugs

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai

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530331, A61K 3800, C07K 523

Patent

active

058800972

ABSTRACT:
Compounds wherein a biologically active molecule is coupled to a glutathione analog through a conjugated system which permits activation of the biologically active molecule while retaining the biologically active molecule tethered to the glutathione analog are useful as tethered prodrugs that slow the rate of clearance of an active biomolecule through the multidrug resistance pump.

REFERENCES:
patent: 5545621 (1996-08-01), Kauvar et al.
patent: 5556942 (1996-09-01), Kauvar et al.
Jedlitschky, G. et al., "ATP-dependent Transport of Glutathione S-Conjugates by the Multidrug Resistance-associated Protein," Cancer Research 54, 4833-4836 (Sep. 15, 1994).
Lyttle, M.H. et al., "Glutathione-S-transferase Activities Novel Aklylating Agents," J. Med. Chem. (1994) 37:1501-1507.
Fenselau, C. et al., "High-performance tandem mass spectrometry in metabolism studies," Xenobiotica (1992) 22(9/10):1207-1219.
Sharer, J. E. et al., "Formation, Stability, and Rearrangements of the Glutathione Conjugates of Butadiene Monoxide: Evidence for the Formation of Stable Sulfurane Intermediates," Chem. Res. Toxicol. (1991) 4(4):430-436.
Akerboom, Th.P.M., et al., "Low- and high-Km transport of dinitrophenyl glutathione in inside of vesicles from human erythrocytes," Biochem Biophys Acta (1992) 1103(1):115-119.
Satiam, A., et al., "Design, Synthesis and Evaluation of Latent Alkylating Agents Activated by Glutathione S-Transferase," (1996) 39:1796-1747.
Bundgaard, H. "Design of Prodrugs" (1985) Elsevier Science Publishers B.V. pp. 1-24.
Silverman, R.B. "The Organic Chemistry of Drug Design and Drug Action" (Academic Press Inc. 1988) pp. 352-401.

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