Design of targeted libraries

Fig. 15.13 General process outline and considerations for design of targeted libraries.

Design of Targeted Libraries Against the Human Chk1 Kinase Using PGVL Hub... 

W Zheng, SI Cho, A Tropsha. Rational combinatorial library design 1. Focus-2D A new approach to the design of targeted combinatorial chemical libraries. J Chem Inf Comput Sci 38 251-258, 1998. 

Historically, ligand structure-based design has been the most widely used approach to the design of target-directed chemical libraries. Methods that start from hits or leads are among the most diverse, ranging from 2D substructure search and similarity-based techniques to analysis of 3D pharmacophores and molecular interaction fields (Fig. 15.2). 

The practical utility of the target-structure-based approach in the design of chemical libraries is still limited because of the requirement of quality crystallographic data, detailed knowledge of the ligand binding mode, and... 

TABLE 15.1 Specialized Computational Technologies for Target Structure-Based Design of Combinatorial Libraries... 

Andrews KM, Cramer RD. Toward general methods of targeted library design topomer shape similarity searching with diverse structures as queries. / Med Chem 2000 43 1723-40. 

Combinatorial approaches have been most successful when information about the target biomole cule has been considered in the design of the library. However, for many biomolecules, structural or mechanistic information is not available or does not provide sufficient insight to enable productive library design Also, lead compounds are not available for many targets, and in some cases, novel motifs for binding are desired. Under these circumstances, it is no surprise that the successful application of combinatorial chemistry has been less fre-... 

In this paper, we elucidated some theoretical and practical aspects in the design of target-specific combinatorial libraries. In the studies we described to illustrate a real... 

The statistics-based approach described consists of a series of automated procedures, is easily reproducible, and can be recommended for the practical design of compound libraries targeted against biotargets, for which sufficiently large number of selective ligands is available. It is important to note that all the procedures described are computationally inexpensive and permit real-time calculations with moderate hardware requirements. 

Cho, S.J., Zheng, W., Teopsha, A. Rational combinatorial library design. 2. Rational design of targeted combinatorial peptide libraries using chemical similarity probe and the inverse QSAR approaches./. Chem. Inf. Comput. Sci. 1998, 38, 259-268. 

---