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Document http://legacy.netlibrary.com/nlreader/nlReader.dll?bookid=12640&filename=Page_568.html (1 of 2) [4/9/2004 1:07:02 AM] Page 568
Document Page 569 molecule. A noncomprehensive listing of such receptor, protease, and signal-transduction protein targets is shown in Table 1. With respect to receptor-targeted peptidomimetic drug discovery, the most noteworthy success has been attained for G-protein-coupled receptor agonists and antagonists as well as, more recently, cell-adhesion integrin receptor antagonists (see below). However, it is important to state that the impact of highthroughput screening in the discovery of nonpeptide ligands (typically antagonists) at G-protein-coupled receptors has yielded extraordinary success. Although screening-based nonpeptide drug discovery will not be extensively reviewed here, the possibility of common pharmacophores between peptide and nonpeptide ligands may exist (limited cases) in relation to receptor binding. Nevertheless, in most cases receptor mutagenesis studies suggest the existence of different binding pockets for peptide and nonpeptide ligands, regardless of whether they both are functionally similar as related to agonism or antagonism [33]. With respect to both protease-and signal-transduction protein-targeted peptidomimetic drug discovery, the emergence of 3D structural information to provide high resolution molecular “maps” of the catalytic (or noncatalytic) domain has provided incredible opportunities for structure-based drug design. II. Peptide Ligand Lead Discovery and Structure-Based Drug Design As stated previously, peptidomimetic drug discovery was first advanced by molecular design concepts and chemical modification strategies focused on http://legacy.netlibrary.com/nlreader/nlReader.dll?bookid=12640&filename=Page_569.html [4/9/2004 1:07:26 AM]
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Structure-based Drug Design 14 Stru
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Document IV. Drug Design Progressio
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Document References 1. Parks RE Jr.
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Page 671 and 672: Document 34. Fei Y-J, Kanai Y, Nuss
Page 673 and 674: Document 21 Structure-Based Combina
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Page 685 and 686: Document Lists of Bonding Fragment
Page 687 and 688: Document Figure 8 Minimized structu
Page 689 and 690: Document Page 555 N-acylpyrrolidine
Page 691 and 692: Document 10. Bobbyer DNA, Goodford
Page 693 and 694: Document structure. 2. Ligand probe
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Page 697 and 698: Document 22 Peptidomimetic and Nonp
Page 699 and 700: Document Figure 1 Examples of nativ
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Page 735 and 736: Document Page 595 the MC1 receptor
Page 739 and 740: Document Figure 22 Protease 3D stru
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Page 743 and 744: Document Page 603 hydroxymethyl sub
Page 745 and 746: Document Page 605 For other serinyl
Page 747 and 748: Document Page 607 scopic studies pr
Page 749 and 750: Document Page 609 (e.g., thermolysi
Page 755 and 756: Document (Ser/Thr) peptide 2.9 Å 2
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Document Acknowledgments Page 620 I
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Document 18. Sawyer TK. In: Peptide
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Document Page 622 Fukuroda T, Fukam
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Document 78. Rodriguez M, Crosby R,
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Document MA, Welch KM, Hallak H, Ta
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Document 97; (e) Fujii I, Nakamura
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Document Med Biol 1991; 306:9-21; (
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Document Page 629 ML, Clare M, Decr
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Document Page 630 177. (a) Bode W,
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Document son AH, Drummond AH, Huxle
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Document Cyclotheonamide A (CtA), 2
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Document D ddI, 152 tumour necrosis
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Document antistasin peptides, 281 c
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Document fragment-based programs, 5
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Document [Human immunodeficiency vi
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Document overview, 103-104, 108-109
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