Burger's Medicinal Chemistry and Drug Discovery vol.4 by Donald J. Abraham

By Donald J. Abraham

This can be quantity four: Autocoids, Diagnostics, and medication from New Biology, of Burger's Medicinal Chemistry and Drug Discovery, sixth version. This new quantity comprises severe new chapters on Peptide and Protein Hormones, Peptide Neurotransmitters, and healing brokers, supplements and SNPs: unmarried Nucleotide Polymorphisms and Pharmacogenomics.

to buy the complete 6 quantity set, please check with ISBN 0-471-37032-0.

for an entire record of articles and participants in addition to unfastened pattern chapters from this new sixth variation please stopover at: www.mrw.interscience.wiley.com/bmcdd

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Extra info for Burger's Medicinal Chemistry and Drug Discovery vol.4 Autocoids, Diagnostics, and Drugs from New Biology

Example text

5) in a large (-1440 A3) convoluted pocket. The thiazolidinedione ring binds in a polar site, making hydrogen bonds with groups in the side chains of His-449, Tyr-473, His-323, and Ser-289. Each of these amino acids forms part of a different helical component of the protein. Agonist binding results in the stabilization of a conformation in which the terminal carboxylate group of the AF-2 helix at the Cterminus of the PPARy LBD is positioned to form hydrogen bonds with elements of the RXR protein in the heterodimer.

PIPARa, -6, and - y are structurally quite simila r, and the agonist-binding conformations of th e LBD are nearly identical. The P P A R y sele,ctivity of the thiazolidinediones manifests SUlbtle differences (206, 207). The binding PCcket of PPARS is narrower in the region of AlF-2 and unable to accommodate the thiazoliclinedione ring or large substituents a to the carbonyl in carboxylic acid head groups. In PI'ARa, substitution of a larger tyrosine for the histamine (His-323)in P P A R y involved in h~rdrogen bonding to the thiazolidinedione Prevents binding.

Bailey, Curr. Opin. Endocrinol. Diabetes, 4,40-47 (1997). 120. A. J. Scheen, Clin. , 30, 359371 (1996). 121. R. A. DeFronzo, A. M. Goodman, and the Multicenter Metformin Study Group, N. Engl. J. , 333,541-549 (1995). 122. I. W . Campbell and H. C. S. Howlett, Diabetes Metab. , 11, S57-S62 (1995). 123. K. Cusi, A. Consoli, and R. A. DeFronzo, J. Clin. Endocrinol. , 81, 4059-4067 (1996). 124. M. Stunvoll, N. Nurjhan, G. Periello, G. Dailey, and J. E. Gerich, N. Engl. J. , 333, 550-554 (1995). 125.

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