Fragmentation approaches, ligand

Fragment-Based Ligand Design Puzzling Approaches to Drug Discovery.126... 

Aronov, A. M. and Bemis, G. W., A minimalist approach to fragment-based ligand design using common rings and linkers application to kinase inhibitors. Proteins, 2004, 57, 36-50. 

A fragment approach to this cluster type is more than an academic exercise to make connections between known clusters. Recognition that the [CN] ligand, which is... 

Fig. 15.2-15 Development of kinase-biased screening libraries during an NMR-based fragment approach. The K, values of the fragments are obtained by quantification of the STD NMR resonances of an adenosine derivative, which is used as the reporter ligand in a competition assay, (a) As a proof of principle, published high-affinity ligands are fragmented into their components. The NMR method is applied to this validation set, which reveals the typical affinities of a particular kinase toward the standard kinase fragments. For example, fragments usually exhibit higher affinities to kinase A...

F. Fragmentation Approach In actual practice, the fragmentation approach affords rather complete flexibility to the ligand and subsequently, bind them at the appropriate target site. 

Ludi Ludi [17] is a product of Acceliys (Insight II) which can be used in both stmc-ture-based dmg design (protein structure is known) and ligand-based drug design (protein stmcture is not known). Based on this, it mns in two modes receptor mode and active analog mode. This mainly follows the fragment approach where initially... 

Soderhjelm P, Aquilante F, Ryde U (2009) Calculation of protein-ligand interaction energies by a fragmentation approach combining high-level quantum chemistry with classical many-body effects. J Phys Chem B 113(32) 11085-11094... 

Tanaka, D., Tsuda, Y., Shiyama, T., Nishimura, T., Chiyo, N., Tominaga, Y., Sawada, N., Mimoto, T., and Kusunose, N. (2011) A practical use of ligand efficiency indices out of the fragment-based approach ligand efficiency-guided lead identification of soluble epoxide hydrolase inhibitors. Journal of Medicinal Chemistry, 54, 851-857. 

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