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Document Figure 5 Secondary structure modifications using β-turn α-turn, and β-sheet scaffolds. Page 566 γ-turn mimetic, 27, illustrates an innovative approach to incorporate a retroamide surrogate between the i and i+1 amino acid residues with an ethylene bridge between the N' (i.e., nitrogen replacing the carbonyl C') and N atoms of the i and i+2 positions, and this template allows the possibility for all three side chains of the parent tripeptide sequence. Finally, the design of a β-sheet mimetic, 28, provides an attractive template to constrain the backbone of a peptide to that simulating an extended conformation [32]. The β-sheet is of particular interest to the area of protease-targeted peptidomimetic drug discovery. http://legacy.netlibrary.com/nlreader/nlReader.dll?bookid=12640&filename=Page_566.html (1 of 2) [4/9/2004 1:01:15 AM]
Document 12640-0567a.gif Figure 6 Contemporary drug discovery: integration of structure-based drug design, synthetic chemical libraries, and high-throughput mass screening technologies Finally, the convergence of structure-based drug design (biophysical and computational chemistry), synthetic chemical libraries, and high-throughput screening technologies have established a new paradigm for drug discovery (Figure 6). This powerful alliance of scientific disciplines is accelerating the identification of lead compounds and/or the optimization of drug candidates. The impact to academic, biotechnological and pharmaceutical research will be immense. C. Receptor, Protease, and Signal Transduction-Protein Targets Page 567 Structure-based drug design and peptidomimetic drug discovery has emerged as a powerful approach in many areas of pharmaceutical research, including receptor agonists and antagonists, protease inhibitors, and, more recently, in the rapidly developing area of signal transduction, in which the protein targets include catalytic and noncatalytic domains of a particular intracellular macro http://legacy.netlibrary.com/nlreader/nlReader.dll?bookid=12640&filename=Page_567.html [4/9/2004 1:04:46 AM]
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Structure-based Drug Design 14 Stru
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Page 693 and 694: Document structure. 2. Ligand probe
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Page 697 and 698: Document 22 Peptidomimetic and Nonp
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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
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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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