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WO1996030849B1 - Determination d'une structure pharmacophore au moyen d'un procede de monte carlo par consensus et biais de configuration - Google Patents

Determination d'une structure pharmacophore au moyen d'un procede de monte carlo par consensus et biais de configuration

Info

Publication number
WO1996030849B1
WO1996030849B1 PCT/US1996/004229 US9604229W WO9630849B1 WO 1996030849 B1 WO1996030849 B1 WO 1996030849B1 US 9604229 W US9604229 W US 9604229W WO 9630849 B1 WO9630849 B1 WO 9630849B1
Authority
WO
WIPO (PCT)
Prior art keywords
compound
compounds
conformational
pharmacophore
structures
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US1996/004229
Other languages
English (en)
Other versions
WO1996030849A1 (fr
Filing date
Publication date
Priority claimed from US08/418,992 external-priority patent/US6341256B1/en
Application filed filed Critical
Priority to AU53246/96A priority Critical patent/AU5324696A/en
Priority to EP96909882A priority patent/EP0826182A1/fr
Publication of WO1996030849A1 publication Critical patent/WO1996030849A1/fr
Publication of WO1996030849B1 publication Critical patent/WO1996030849B1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Abstract

Dans un mode de réalisation spécifique, l'invention concerne un procédé de sélection de composés principaux extrêmement ciblés afin de créer un médicament se fixant à une molécule cible. Ce procédé consiste à cribler une banque de diversités contre la molécule cible afin de recueillir les éléments de fixation sélective. On examine ensuite la structure des éléments sélectionnés et on détermine un candidat pharmacophore responsable de la fixation à la molécule cible. On détermine ensuite, de préférence, par résonance magnétique nucléaire REDOR, plusieurs distances interatomiques extrêmement précises dans certains des éléments sélectionnés en relation avec le candidat pharmacophore. On effectue une détermination de la structure du candidat pharmacophore au moyen d'un procédé de Monte Carlo par consensus extrêmement précis et biais de configuration, en utilisant la structure des éléments sélectionnés et en incorporant en tant que contraintes le candidat pharmacophore partagé et les distances mesurées. Cette détermination est conçue pour examiner efficacement uniquement des configurations à énergie relativement basse tout en respectant toutes contraintes structurelles présentes dans la banque de diversités organiques. Si la banque de diversités contient des peptides courts, la détermination respecte les degrés connus de liberté des peptides ainsi que toutes contraintes internes, telles que celles qui sont imposées par des ponts disulfure. Enfin, on utilise le pharmacophore extrêmement précis déterminé de cette façon, afin de sélectionner des composés organiques principaux pour créer un médicament ciblé au niveau de la molécule cible initiale.
PCT/US1996/004229 1995-03-31 1996-03-27 Determination d'une structure pharmacophore au moyen d'un procede de monte carlo par consensus et biais de configuration Ceased WO1996030849A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
AU53246/96A AU5324696A (en) 1995-03-31 1996-03-27 Consensus configurational bias monte carlo method and system for pharmacophore structure determination
EP96909882A EP0826182A1 (fr) 1995-03-31 1996-03-27 Determination d'une structure pharmacophore au moyen d'un procede de monte carlo par consensus et biais de configuration

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US418,992 1995-03-31
US08/418,992 US6341256B1 (en) 1995-03-31 1995-03-31 Consensus configurational bias Monte Carlo method and system for pharmacophore structure determination

Publications (2)

Publication Number Publication Date
WO1996030849A1 WO1996030849A1 (fr) 1996-10-03
WO1996030849B1 true WO1996030849B1 (fr) 1996-11-14

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1996/004229 Ceased WO1996030849A1 (fr) 1995-03-31 1996-03-27 Determination d'une structure pharmacophore au moyen d'un procede de monte carlo par consensus et biais de configuration

Country Status (5)

Country Link
US (2) US6341256B1 (fr)
EP (1) EP0826182A1 (fr)
AU (1) AU5324696A (fr)
CA (1) CA2216994A1 (fr)
WO (1) WO1996030849A1 (fr)

Families Citing this family (33)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0905512A1 (fr) * 1997-09-25 1999-03-31 Cerep Méthode pour l'identification des structures de base ou composés actifs
US6168913B1 (en) * 1997-10-14 2001-01-02 Abbott Laboratories Coding combinatorial libraries with fluorine tags
US6990221B2 (en) * 1998-02-07 2006-01-24 Biodiscovery, Inc. Automated DNA array image segmentation and analysis
US20050112607A1 (en) * 1999-01-23 2005-05-26 Bamdad Cynthia C. Rapid and sensitive detection of protein aggregation
PT1144607E (pt) * 1999-07-20 2009-04-22 Morphosys Ag Novos métodos para apresentar (poli)peptídeos/ proteínas em partículas bacteriofágicas através de ligações dissulfureto
US6677160B1 (en) 1999-09-29 2004-01-13 Pharmacia & Upjohn Company Methods for creating a compound library and identifying lead chemical templates and ligands for target molecules
US6764858B2 (en) 1999-09-29 2004-07-20 Pharmacia & Upjohn Company Methods for creating a compound library
US7099502B2 (en) * 1999-10-12 2006-08-29 Biodiscovery, Inc. System and method for automatically processing microarrays
CA2405715C (fr) * 2000-04-14 2011-11-15 Genencor International, Inc. Methodes de ciblage selectif
WO2002039087A2 (fr) * 2000-11-02 2002-05-16 Protein Mechanics, Inc. Procede d'utilisation de longs intervalles de temps en modelisation moleculaire
US20030068650A1 (en) * 2001-03-12 2003-04-10 Jack Greenblatt Target analysis for chemistry of specific and broad spectrum anti-infectives and other therapeutics
WO2002073373A2 (fr) * 2001-03-12 2002-09-19 Board Of Regents, University Of Texas System Strategie basee sur des ensembles permettant d'elaborer des produits pharmaceutiques a base de proteines
AU2002356864A1 (en) * 2001-10-29 2003-05-12 Vertex Pharmaceuticals Incorporated Processes for producing optimized pharmacophores
US20030139907A1 (en) * 2002-01-24 2003-07-24 Mccarthy Robert J System, Method, and Product for Nanoscale Modeling, Analysis, Simulation, and Synthesis (NMASS)
US20040015299A1 (en) * 2002-02-27 2004-01-22 Protein Mechanics, Inc. Clustering conformational variants of molecules and methods of use thereof
US20030171873A1 (en) * 2002-03-05 2003-09-11 Bruce Hoff Method and apparatus for grouping proteomic and genomic samples
WO2003083438A2 (fr) * 2002-03-26 2003-10-09 Carnegie Mellon University Procedes et systemes de modelisation moleculaire
US20050181464A1 (en) * 2002-04-04 2005-08-18 Affinium Pharmaceuticals, Inc. Novel purified polypeptides from bacteria
CA2492041A1 (fr) * 2002-07-01 2004-01-08 3-Dimensional Pharmaceuticals, Inc. Echantillonnage conformationnel par auto-organisation
US7512496B2 (en) * 2002-09-25 2009-03-31 Soheil Shams Apparatus, method, and computer program product for determining confidence measures and combined confidence measures for assessing the quality of microarrays
US20040267456A1 (en) * 2003-06-27 2004-12-30 Stephan Brunner Method and computer program product for drug discovery using weighted grand canonical metropolis Monte Carlo sampling
US7415361B2 (en) * 2003-12-09 2008-08-19 Locus Pharmaceuticals, Inc. Methods and systems for analyzing and determining ligand-residue interaction
US20050177318A1 (en) * 2004-02-10 2005-08-11 National Institute Of Statistical Sciences Methods, systems and computer program products for identifying pharmacophores in molecules using inferred conformations and inferred feature importance
US20050222776A1 (en) * 2004-03-31 2005-10-06 Locus Pharmaceuticals, Inc. Method for fragment preparation
EP2190987B1 (fr) * 2007-08-21 2012-11-14 MorphoSys AG Procédés permettant la formation de liaisons disulfure
GB0816100D0 (en) * 2008-09-04 2008-10-15 Univ Bristol Molecular structure determination from nmr spectroscopy
US9568574B2 (en) * 2012-03-12 2017-02-14 Bruker Biospin Corporation Pulse sequence for homonuclear J-decoupling during NMR data acquisition
CN102930152B (zh) * 2012-10-26 2016-08-03 中国科学院上海药物研究所 一种模拟配体分子与靶标受体反应并计算预测该反应的热力学与动力学参数的方法和系统
US20160131603A1 (en) * 2013-06-18 2016-05-12 The George Washington University a Congressionally Chartered Not-for-Profit Corporation Methods of predicting of chemical properties from spectroscopic data
DE102014202649B4 (de) * 2014-02-13 2015-12-10 Siemens Aktiengesellschaft Leise MR-Bildgebung durch eine variable Anzahl von Pulssequenzabschnitten zwischen zwei Vorpulsen
US10426424B2 (en) 2017-11-21 2019-10-01 General Electric Company System and method for generating and performing imaging protocol simulations
CN112461881B (zh) * 2020-10-16 2022-02-18 北京大学 一种检测rna中弱稳定性碱基对的固体核磁共振方法
CN117347415B (zh) * 2023-09-22 2024-10-01 江苏国源先进仪器技术研究院有限公司 一种基于高场核磁共振技术鉴定多肽药物二硫键的方法

Family Cites Families (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5225533A (en) 1988-05-02 1993-07-06 The Regents Of The University Of California General method for producing and selecting peptides with specific properties
US5025388A (en) 1988-08-26 1991-06-18 Cramer Richard D Iii Comparative molecular field analysis (CoMFA)
ATE168416T1 (de) 1989-10-05 1998-08-15 Optein Inc Zellfreie synthese und isolierung von genen und polypeptiden
US5252743A (en) 1989-11-13 1993-10-12 Affymax Technologies N.V. Spatially-addressable immobilization of anti-ligands on surfaces
JPH05503691A (ja) * 1989-12-29 1993-06-17 ユニバーシティ・テクノロジーズ・インターナショナル・インコーポレイテッド アゴニストおよびアンタゴニストを含む生物学的に活性なリガンドの３次構造モデルの設計方法およびアンギオテンシンに基づいた新規合成アンタゴニスト
US5747334A (en) 1990-02-15 1998-05-05 The University Of North Carolina At Chapel Hill Random peptide library
US5265030A (en) * 1990-04-24 1993-11-23 Scripps Clinic And Research Foundation System and method for determining three-dimensional structures of proteins
US5331573A (en) 1990-12-14 1994-07-19 Balaji Vitukudi N Method of design of compounds that mimic conformational features of selected peptides
US5270170A (en) 1991-10-16 1993-12-14 Affymax Technologies N.V. Peptide library and screening method
US5348867A (en) 1991-11-15 1994-09-20 George Georgiou Expression of proteins on bacterial surface
US5241470A (en) 1992-01-21 1993-08-31 The Board Of Trustees Of The Leland Stanford University Prediction of protein side-chain conformation by packing optimization
WO1993017032A1 (fr) 1992-02-24 1993-09-02 The Trustees Of The University Of Pennsylvania Techniques et intermediaires de preparation de peptidomimetismes non peptidiques
US5573905A (en) 1992-03-30 1996-11-12 The Scripps Research Institute Encoded combinatorial chemical libraries
US5434796A (en) * 1993-06-30 1995-07-18 Daylight Chemical Information Systems, Inc. Method and apparatus for designing molecules with desired properties by evolving successive populations
US5740072A (en) * 1994-10-07 1998-04-14 The Trustees Of Columbia Universuty In The City Of New York Rapidly convergent method for boltzmann-weighted ensemble generation in free energy simulations
US5680319A (en) * 1995-05-25 1997-10-21 The Johns Hopkins University School Of Medicine Hierarchical protein folding prediction

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