Novo Ligand Design

Allen and O. Kennard, Chem. Design Automat. News, 

Lico and Y. Martin, Abstracts of Papers of the American Chemical Society , 1995, 210, No. Ptl, Pp.9-Comp. 

One of the most important goals of research in medicinal chemistry is to discover new small molecules that bind to a protein or to other biopolymeric structures of pharmacological interest. In particular, enzymes that regulate biochemical reactions are important targets in contemporary medicinal chemistry. Compounds binding specifically to one of these targets can be useful in the treatment of various diseases. 

It has been demonstrated for a large number of different molecular targets that the 3D structure of the protein, which is obtained by X-ray crystallography or NMR spectroscopy, can be used to design novel ligands, This structure-based design has led to many useful new structures that were tested in clinical trials. The carbonic anhydrase inhibitor dor-zolamide, marketed since 1995, is probably the first drug 

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B and W J Howe 1991. Computer Design of Bioactive Molecules - A Method for Receptor-Based Novo Ligand Design. Proteins Structure, Function and Genetics 11 314-328. i H L 1965. The Generation of a Unique Machine Description for Chemical Structures - A hnique Developed at Chemical Abstracts Service. Journal of Chemical Documentation 5 107-113. J 1995. Computer-aided Estimation of Symthetic Accessibility. PhD thesis. University of Leeds, itan R, N Bauman, J S Dixon and R Venkataraghavan 1987. Topological Torsion A New )lecular Descriptor for SAR Applications. Comparison with Other Descriptors. Journal of emical Information and Computer Science 27 82-85. 

Boehm H-J. Fragment-based de novo ligand design. Proceedings of the Alfred Benzon Symposium No. 39,1996. p. 402-13. 

Bohm HJ. Current computational tools for de novo ligand design. Curr Opin Biotechnol 1996 7 433 436. 

Shukla RB, Kumar K, Weber R, Zhang X, Tweedle M (1997) Alteration of electronic relaxation in MR contrast agents through de-novo ligand design. Acta Radiol Suppl. 38(S412) 121-123. 

Moon, J.B. and Howe, W.J. Computer design ofbioactive molecules a method for receptor-based de novo ligand design. Proteins Struc., Func., Genet. 1991, 11, 314-328. 

Todorov, N. P., Dean, R. M. (1997) Evaluation of a method for controlling molecular scaffold diversity in de novo ligand design. J Comput Aided Mol Des 11, 175-192. 

Because there are no known leads that bind to the selectivity region of TIM, the design of selective inhibitors is an exercise in de novo ligand design. We tried to... 

Programs for de novo ligand design based on receptor structure... 

Mancera, R. L. (2002) De novo ligand design with explicit water molecules an application to bacterial neuraminidase. J. Comput. Aided Mol. Des. 16,479-499. 

Gillespie, A.M. and White, D.P. (2001) Understanding the steric control of stereoselective olefin binding in cyclopentadienyl complexes of rhenium an application of de novo ligand design. Organometallics, 20, 5149. 

Caflisch, A. and Karplus, M. (1995) Computational combinatorial chemistry for de novo ligand design review and assessment. Persp. Drug Disc. Design, 3, 51. 

Both place c join and incremental construction originated from the area of de novo ligand design.16,85 Moon and Howe90 created the peptide design... 

Methods for treating these problems have emerged from the area of molecular docking and de novo ligand design (see, e.g., Kubinyi158 for an overview on combinatorial docking methods). 

Design of Bioactive Molecules A Method for Receptor-Based De Novo Ligand Design. 

DA Pearlman, MA Murcko (1996) CONCERTS Dynamic Connection of Fragments as an Approach to de Novo Ligand Design, J Med Chem 39(8) 1651—1663... 

Muecko, M.A., An Introduction to de Novo Ligand Design in Practical Application of Computer-Aided Drug Design Char-ifson, P. S. (ed.), Marcel Dekker Inc., New York, 1997. 

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