Mechanism-based design

Tanaka K, Miura T, Umezawa N, Urano Y, Kikuchi K, Higuchi T, Nagano T (2001) Rational design of fluorescein-based fluorescence probes. Mechanism-based design of a maximum fluorescence probe for singlet oxygen. J Am Chem Soc 123 2530-2536... 

Keywords Src Src family kinases Kinase selectivity Structure-based design Mechanism-based design... 

Saponification of the bicyclic p-lactam 21 to yield 22 has been employed by Corey [65] as an experimental evidence of the mechanism-based design of... 

Sandanayaka VP, Prashad AS. Resistance to beta-lactam antibiotics structure and mechanism based design of beta-lactamase inhibitors. Curr Med Chem. 2002 9 1145-1165. 

O Neill, P. M. Bishop, L. R Storr, R. C. Hawley, S. R. Maggs, J. L. Ward, S. A. Park, B. K. Mechanism-based design of parasite-targeted artemisinin derivatives Synthesis... 

Posner, G. H. Oh, C. H. Wang, D. Gerena, L. Milhous, W. K. Meshnick, S. R. Asawamahasadka, W. Mechanism-based design, synthesis, and in vitro antimalarial testing of new 4-methylated trioxanes structurally related to artemisinin The importance of a carbon-centered radical for antimalarial activity. J. Med Chem., 1994, 37(9) 1256-1258. 

Zheng, F., Zhang, C.-G. (2008). Structure-and-mechanism-based design and discovery of therapeutics for cocaine overdose and addiction. Org. Biomol. Chem. 6 836-43. 

Parang K, Till JH, Ablooglu AJ, Kohanski RA, Hubbard SR, Cole PA. Mechanism-based design of a protein kinase inhibitor. Nat. Struct. Biol. 2001 8 37-41. 

Wei Zhao obtained his BS in chemistry (1999) from Shandong University and his Ph.D. in environmental chemistry (2005) from the Research Center for Eco-Environmental Sciences (RCEES), Chinese Academy of Sciences. He is currently an associate professor in the College of Pharmacy at Nankai University, China. His research interests include gly-coscience with an emphasis on carbohydrate chemistry, glycopharmaceutical science, carbohydrate-based vaccines, drugs and immunotherapy, as well as the structural and mechanism-based design and synthesis of inhibitors and ligands. 

Figure 13 Chemical structures of mechanism-based designed bisubstrate analog inhibitors of protein kinase.

Scheme 7-22 Mechanism-based design of golfomycin A (87) (Nicolaou et al.).

Much research has been conducted to generate catalysts that form polypropylenes containing microstructures and architectures that can be rationally controlled. This catalyst development has involved some of the most elegant mechanism-based design of catalysts in any area of organometallic chemistry. This section describes some of the basic principles that explain how the stereochemistry of polyolefins is controlled. 

Paulay, T. 1998. A mechanism-based design strategy for torsional seismic response of ductile buildings. European Earthquake Engineering 2 33-48. 

Protein engineering has to date been tackled according to two quite different philosophies. The first of these can broadly be termed mechanism-based design. This involves describing protein function as completely as possible so that desired changes can be effected by calculation fiom first principles. Typically the protein mechanic first asks what tiiree dimensional structure an amino acid sequence will adopt, then what function will be performed by such a structure and finally how alterations to the structure may... 

The surface-preparation issue is just as serious for fibrous composite structures (see [2]) as for ones made from metal, and is addressed in other chapters of these volumes. Cleanliness alone is not sufficient the adhesive must want to adhere to the substrate, so the surface must be activated appropriately. No glue will bond to a totally inert surface (see [3]). It suffices to say, here, that all the mechanics-based design procedures are rendered worthless if the glue does not stay stuck ... 

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