Method to design therapeutically important compounds

Details Method to design therapeutically important compounds Method to design therapeutically important compounds

2005-09-20

2005-09-20

Brusca, John S. (Department: 1631)

Data processing: measuring, calibrating, or testing

Measurement system in a specific environment

Chemical analysis

C703S011000

Reexamination Certificate

active

06947847

ABSTRACT:
Disclosed is are methods of generating chemical structures of putative non-peptide inhibitors of biologically-active receptors. The method includes constructing a model of a receptor-ligand complex using empirical three-dimensional data of the receptor-ligand complex. The conformation of the binding site between the receptor and the ligand is then altered to yield novel conformations not exhibited in either the native receptor or the bound receptor. These conformations are then used to generate models of non-peptide chemical structures that are complementary in structure to the altered conformations of the binding site. In this fashion, chemical structures of putative non-peptide inhibitors of the altered conformation are revealed.

REFERENCES:
patent: WO 02/088101 (2002-11-01), None
Carlson et al. Accommadating Protein Flexibility in Computational Drug Design. Mol. Pharmacol. vol. 57, pp. 213-281, (2000).
Abad-Zapatero et al. (1990)Proteins: Struct., Funct., Genet.8:62-81.
Babine & Bender (1997)Chem. Rev.97:1359-1472.
Bohacek & McMartin (1992)J. Med. Chem.35:1671-1684.
Bohacek & McMartin (1994)J. Am. Chem. Soc.116:5560-5571.
Bohacek, McMartin, & Guida (1996)Med Res. Rev.16(1):3-50.
Böhm (1992) “LUDI: rule-based automatic design of new substituents for enzyme inhibitor leads,”J. Comp.-Aided Mol. Des.6:593-606.
Böhm (1992) “The computer program LUDI: a new method for the de novo design of enzyme inhibitors,”J. Comp.-Aided Mol. Des.6:61-78.
Bursavich, West, & Rich (2001)Org. Lett.3(15):2317-2320.
Carter & Wells (1987)Science237:394-399.
Clackson & Wells (1995)Science267:383-386.
DeLucca et al. (1997)Drug Discov. Today2: 6-18.
Eisen et al. (1994) “Hook: A program for finding novel molecular architectures that satisfy the chemical and steric requirements of a macromolecule binding site,”Proteins: Struct., Funct., Genet.19:199-221.
Farmer, “Bridging the gap between bioactive peptides and nonpeptides: some perspectives in design,” inDrug Design;Ariens, E. J., Ed.; Academic Press: New York; vol. 10, pp. 119-143 (1980).
Flentke et al. (1999)Protein Expression&Purif.16:213-220.
Fletcher & Campbell (1998)Chem. Rev.98:763-795.
Gillet et al. (1995) “Sprout, Hippo and CAESA: tools for de novo structure generation and estimation of synthetic accessibility,”Perspect. In Drug Discovery&Des.3:34-50.
Gilliland et al. (1990)Proteins: Struct., Funct., Genet.8:82-101.
Goodfod, P. J. (1985)J. Med. Chem.28:849-857.
Groves et al. (1998)Protein Eng.11(10):833-840.
Güller et al. (1999)Bioorg.&Med. Chem. Lett.9:1403-1408.
Hart & Rich, “Stereochemical aspects of drug action I: Conformational restriction, steric hindrance and hydrophobic collapse,” inPract. Of Med. Chem.;Wermuth, C., Ed.; Acad. Press: London, UK, 1996; pp. 393-412.
Hellinga & Richards (1991)J. Mol. Biol.222:763-785.
Hellinga, Caradonna, & Richards (1991)J. Mol. Biol.222:787-803.
Ho & Marshall (1993) “Splice: a program to assemble partial query solutions from three-dimensional database searches into novel ligands,”J. Comput.-Aided Mol. Des.7:623-647.
Inooka et al. (2001)Nature Structural Biology8(2):161-165.
James, Hsu, & Delabaere (1977)Nature267:808-813.
James et al. (1982)Proc. Natl. Acad. Sci. U. S. A.79:6137-6141.
James & Sielecki (1983)J. Mol. Biol.163:299-361.
Koshland (1958)Proc. Natl. Acad. Sci. U. S. A.44:98-104.
Kumar et al. (1999)Cell Biochem. and Biophys.31:141-164.
Lam et al. (1996)J. Med. Chem.39:3514-3525.
Lauri & Bartlett (1994) “Caveat: a program to facilitate the design of organic molecules,”J. of Comput.-Aided Mol. Des.8:51-66.
Lebon & Ledocq (2000)Curr. Med. Chem.7:455-477.
Lien, Gao, & Lien (1994)Progress in Drug Research43:43-86.
Ma et al. (1999)Proteins Eng.12:713-720.
Märki et al. (2001)Il Farmaco56:21-27.
Martin et al. (1999)Biochemistry38:7978-7988.
Moon & Howe (1991) “Computer design of bioactive molecules: a method for receptor-based de novo ligand design,”Proteins11:314-328.
Newman et al.(1991)J. Mol. Biol.221:1295-1309.
Nishibata & Itai (1991)Tetrahedron47(43):8985-8990.
Northrop (2001)Acc. Chem. Res.34:790-797.
Oefner et al. (1999)Chem.&Biol.6:127-131.
Olson et al. (1993)J. of Med. Chem.36(21):3039-3049.
Piana et al. (2001)J. Am. Chem. Soc.123:8730-8737.
Peranteau et al. (1995)Anal. Biochem.227:242-245.
Rahuel, J., et al. (2000)Chem. Biol.7:493-504.
Rich et al. (1991).J. Med. Chem.34:1222-1225.
Rich et al., inMedicinal Chemistry into the Millennium;Campbell, M. M., Blagbrough, I. S., Eds.; Royal Society of Chemistry, Publ.: Cambridge UK, 2001; pp 16-24.
Ripka & Rich (1998)Curr. Op. in Chem. Biol.2:441-452.
Rotstein & Murcko (1993) “GroupBuild: a fragment-based method for de novo drug design,”J. Med. Chem.36:1700-1710.
Rotstein & Murcko (1993)J. of Comput.-Aided Mol. Des.7:23-43.
Singh, Saldanha, & Thornton (1991) “A novel method for the modeling of peptid ligands to their receptors,”Protein Eng.4(3):251-261.
Sowdhamini et al. (1995)Pharm. Acta Helv.69:185-192.
Spatola, “Peptide backbone modifications; a structure-activity analysis of peptides containing amide bond surrogates, conformational constraints, and related backbone replacements” inChem. Biochem. Amino Acids, Pept., Proteins;Weinstein, B., Ed.; Marcel Dekker, Inc: New York, 1983; pp. 267-357.
Straub (1964)Advan. Enzymol.26:89-114.

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