Glossary of Terms Used in Combinatorial Chemistry

Introduction: The development of combinatorial chemistry has generated a wide variety of new concepts and much associated terminology. In addition, the nature of research in this area has brought together scientists from diverse backgrounds: statisticians may discuss their work with biologists and heterocyclic chemists; medicinal chemists are talking to engineers, analytical chemists, and polymer scientists. In recognition of the potential for confusion and lack of communication in this field, the International Union of Pure and Applied Chemistry (IUPAC) convened a working party (within the Division of Human Health, Medicinal Chemistry Section) to attempt to capture and define the terminology at the interface of these endeavours. The following Glossary is the result of their efforts. It is hoped that it will provide a resource for those new to the area encountering terms for the first time, and, perhaps, to increase the clarity of communication between more experienced workers in the field. The Glossary is not intended as a comprehensive review or encyclopaedia of combinatorial chemistry, although occasional attempts have been made to broaden the scope beyond a strict dictionary-type definition of terms by providing illustrative examples of some terms, and directing readers to literature sources where appropriate. These references have not necessarily been chosen to attribute credit for the discovery or invention of a term; rather they should provide the most pertinent information for the topic. Ideally this will be an article or review with the Glossary term as its central theme, in which proper accreditation for the seminal contributions to that area may be found. Because of the intrinsic interdisciplinary nature of this area of research, it has not been possible to provide a comprehensive coverage of each of the sub-fields, neither has this been the intent. Rather it has been attempted to identify those elements which are particularly pertinent to combinatorial chemistry. Thus, in the analytical sciences "magic angle spinning" gains an entry whereas "mass spectrometry" does not. The interested reader will readily be able to find more detailed treatments of these specialized areas. Trademarks have been included where, in the judgement of the authors, their use has become sufficiently widespread that they often do not receive appropriate citation; the implicit assumption being that the reader will understand what is meant. This criterion has been adopted over one of inclusiveness, which would rapidly become extreme in many areas. In a field which is developing as rapidly as combinatorial chemistry a document such as this Glossary may soon require revision. The authors welcome suggestions for new terms, clarifications, references, and other comments which will aid in the development of this resource.

[1]  D C Spellmeyer,et al.  Discovery of nanomolar ligands for 7-transmembrane G-protein-coupled receptors from a diverse N-(substituted)glycine peptoid library. , 1994, Journal of medicinal chemistry.

[2]  J. Szostak,et al.  In vitro selection of RNA molecules that bind specific ligands , 1990, Nature.

[3]  R. Houghten General method for the rapid solid-phase synthesis of large numbers of peptides: specificity of antigen-antibody interaction at the level of individual amino acids. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[4]  Mark A. Murcko,et al.  Virtual screening : an overview , 1998 .

[5]  J. Labadie,et al.  On the Development of New Poly(styrene-oxyethylene) Graft Copolymer Resin Supports for Solid-Phase Organic Synthesis , 1999 .

[6]  J. Morken,et al.  Thermographic selection of effective catalysts from an encoded polymer-bound library , 1998, Science.

[7]  P. Seneci,et al.  Solid-Supported Benzotriazoles: Synthetic Auxiliaries and Traceless Linkers for the Combinatorial Synthesis of Amine Libraries1 , 1999 .

[8]  M. Mutter,et al.  Liquid Phase Synthesis of Peptides , 1972, Nature.

[9]  Y. Oda,et al.  DIRECT MONITORING OF ORGANIC REACTIONS ON POLYMERIC SUPPORTS , 1997 .

[10]  Johann Gasteiger,et al.  Neural Networks for Chemists: An Introduction , 1993 .

[11]  Roger E. Critchlow,et al.  Beyond mere diversity: tailoring combinatorial libraries for drug discovery. , 1999, Journal of combinatorial chemistry.

[12]  H. Pedersen,et al.  Selenium-Linking Strategy for Traceless Solid-Phase Synthesis: Direct Loading, Aliphatic C−H Bond Formation upon Cleavage and Reaction Monitoring by Gradient MAS NMR Spectroscopy , 1998 .

[13]  Michael C. Pirrung Spatially Addressable Combinatorial Libraries , 1997 .

[14]  J. C. Hodges,et al.  Polymer‐Supported Quenching Reagents for Parallel Purification. , 1997 .

[15]  Abdelazize Laoui,et al.  DIVSEL and COMPLIB - Strategies for the Design and Comparison of Combinatorial Libraries using Pharmacophoric Descriptors , 1998, J. Chem. Inf. Comput. Sci..

[16]  D A Konings,et al.  Deconvolution of combinatorial libraries for drug discovery: a model system. , 1995, Journal of medicinal chemistry.

[17]  Jonathan A. Ellman,et al.  Design, Synthesis, and Evaluation of Small-Molecule Libraries , 1996 .

[18]  L. Gold,et al.  Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. , 1990, Science.

[19]  R. Barrett,et al.  Peptides on phage: a vast library of peptides for identifying ligands. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[20]  Edward S. Wilks,et al.  Dendritic and Star Polymers: Classification, Nomenclature, Structure Representation, and Registration in the DuPont SCION Database , 1998, J. Chem. Inf. Comput. Sci..

[21]  E. Bayer Towards the Chemical Synthesis of Proteins , 1991 .

[22]  David C Schriemer,et al.  Micro-Scale Frontal Affinity Chromatography with Mass Spectrometric Detection: A New Method for the Screening of Compound Libraries. , 1998, Angewandte Chemie.

[23]  S M Freier,et al.  Deconvolution of combinatorial libraries for drug discovery: experimental comparison of pooling strategies. , 1996, Journal of medicinal chemistry.

[24]  M. Pirrung,et al.  PREPARATION AND SCREENING AGAINST ACETYLCHOLINESTERASE OF A NON-PEPTIDE INDEXED COMBINATORIAL LIBRARY , 1995 .

[25]  Kit S. Lam,et al.  The “One-Bead-One-Compound” Combinatorial Library Method , 1997 .

[26]  Yvonne C. Martin,et al.  Use of Structure-Activity Data To Compare Structure-Based Clustering Methods and Descriptors for Use in Compound Selection , 1996, J. Chem. Inf. Comput. Sci..

[27]  J. Liu,et al.  DNA binding by an amino acid residue in the C-terminal half of the Rel homology region. , 1994, Chemistry & biology.

[28]  Jürgen Bajorath,et al.  Identification of a Preferred Set of Molecular Descriptors for Compound Classification Based on Principal Component Analysis , 1999, J. Chem. Inf. Comput. Sci..

[29]  M. Navre,et al.  Identification of highly selective inhibitors of collagenase-1 from combinatorial libraries of diketopiperazines. , 1999, Journal of medicinal chemistry.

[30]  D. Flynn,et al.  In Situ Chemical Tagging: Tetrafluorophthalic Anhydride as a “Sequestration Enabling Reagent” (SER) in the Purification of Solution-Phase Combinatorial Libraries , 1997 .

[31]  S J Rodda,et al.  A priori delineation of a peptide which mimics a discontinuous antigenic determinant. , 1986, Molecular immunology.

[32]  Dennis P Curran,et al.  Strategy-Level Separations in Organic Synthesis: From Planning to Practice. , 1998, Angewandte Chemie.

[33]  Miles G. Siegel,et al.  Use of solid supported nucleophiles and electrophiles for the purification of non-peptide small molecule libraries , 1996 .

[34]  D. Hawkins,et al.  Analysis of a 2(9) full factorial chemical library. , 1995, Journal of medicinal chemistry.

[35]  M. Schroeder,et al.  "Diversomers": an approach to nonpeptide, nonoligomeric chemical diversity. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[36]  Robert P. Sheridan,et al.  Using a Genetic Algorithm To Suggest Combinatorial Libraries , 1995, J. Chem. Inf. Comput. Sci..

[37]  P. Griffin,et al.  Dendrimer-supported combinatorial chemistry. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[38]  Clemencia Pinilla,et al.  A review of the utility of soluble peptide combinatorial libraries , 1995, Biopolymers.

[39]  J. Scott,et al.  Searching for peptide ligands with an epitope library. , 1990, Science.

[40]  A. W. Czarnik,et al.  Encoding methods for combinatorial chemistry. , 1997, Current opinion in chemical biology.

[41]  P. Schultz,et al.  A Class of Cobalt Oxide Magnetoresistance Materials Discovered with Combinatorial Synthesis , 1995, Science.

[42]  Combinatorial libraries by portioning and mixing. , 1999, Combinatorial chemistry & high throughput screening.

[43]  Xin Chen,et al.  Recursive Partitioning Analysis of a Large Structure-Activity Data Set Using Three-Dimensional Descriptors1 , 1998, J. Chem. Inf. Comput. Sci..

[44]  P. Willett Genetic algorithms in molecular recognition and design. , 1995, Trends in biotechnology.

[45]  H. Coste,et al.  Orthogonal Combinatorial Chemical Libraries , 1995 .

[46]  M. Sung,et al.  X-ray Photoelectron Spectroscopy Analysis of Solid-Phase Reactions Using 3-Brominated Wang Resin , 1999 .

[47]  S. Brenner,et al.  Recursive deconvolution of combinatorial chemical libraries. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[48]  M. Wigler,et al.  Complex synthetic chemical libraries indexed with molecular tags. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[49]  E. Kaiser,et al.  Color test for detection of free terminal amino groups in the solid-phase synthesis of peptides. , 1970, Analytical biochemistry.

[50]  Stephen B. H. Kent,et al.  Efficient method for the preparation of peptoids [oligo(N-substituted glycines)] by submonomer solid-phase synthesis , 1992 .

[51]  John Bradshaw,et al.  The Effectiveness of Reactant Pools for Generating Structurally-Diverse Combinatorial Libraries , 1997, J. Chem. Inf. Comput. Sci..

[52]  C. Holmes,et al.  Methods for Combinatorial Organic Synthesis: The Use of Fast 13C NMR Analysis for Gel Phase Reaction Monitoring , 1994 .

[53]  P. Bartlett,et al.  Synthetic strategies in combinatorial chemistry. , 1997, Current opinion in chemical biology.

[54]  Svante Wold,et al.  Multivariate Parametrization of 55 Coded and Non‐Coded Amino Acids , 1989 .

[55]  Rees,et al.  Molecular diversity and its analysis. , 1999, Drug discovery today.

[56]  R. Sheppard,et al.  The safety catch principle in solid phase peptide synthesis , 1971 .

[57]  J. C. Hodges,et al.  Solid‐Supported Reagent Strategies for Rapid Purification of Combinatorial Synthesis Products , 1999 .

[58]  E. Gordon,et al.  Combinatorial chemistry and molecular diversity in drug discovery , 1998 .

[59]  J. Davies Solid Phase Peptide Synthesis , 1995 .

[60]  Andrew D. Ellington,et al.  Nucleic Acid Selection and the Challenge of Combinatorial Chemistry , 1997 .

[61]  S. Daniels,et al.  A comparison of acid labile linkage agents for the synthesis of peptide C-terminal amides , 1989 .

[62]  Michael B. Hall,et al.  Dendritic macromolecules: synthesis of starburst dendrimers , 1986 .

[63]  D. A. Campbell,et al.  A simple procedure for the solid phase synthesis of diketopiperazine and diketomorpholine derivatives , 1997 .

[64]  D. Hudson,et al.  Matrix assisted synthetic transformations: a mosaic of diverse contributions. I. The pattern emerges. , 1999, Journal of combinatorial chemistry.

[65]  H. Rink Solid-phase synthesis of protected peptide fragments using a trialkoxy-diphenyl-methylester resin. , 1987 .

[66]  J. Baldwin,et al.  Synthesis of a Small Molecule Combinatorial Library Encoded with Molecular Tags , 1995 .

[67]  J. Ellman,et al.  Germanium and Silicon Linking Strategies for Traceless Solid-Phase Synthesis. , 1997, The Journal of organic chemistry.

[68]  B. E. Evans,et al.  Methods for drug discovery: development of potent, selective, orally effective cholecystokinin antagonists. , 1988, Journal of medicinal chemistry.

[69]  R. Nachbar,et al.  Two new criteria for choosing sample size in combinatorial chemistry. , 1996, Journal of medicinal chemistry.

[70]  Nolan,et al.  Flow cytometry: a versatile tool for all phases of drug discovery. , 1999, Drug discovery today.

[71]  S. Brenner,et al.  Liquid-phase combinatorial synthesis. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[72]  R. B. Merrifield Solid phase peptide synthesis. I. the synthesis of a tetrapeptide , 1963 .

[73]  A. Eliseev,et al.  Use of Molecular Recognition To Drive Chemical Evolution: Mechanisms of an Automated Genetic Algorithm Implementation , 1998 .

[74]  David C. Sherrington,et al.  PREPARATION, STRUCTURE AND MORPHOLOGY OF POLYMER SUPPORTS , 1999 .

[75]  T. Lowary,et al.  Oligosaccharide Mimetics Obtained by Novel, Rapid Screening of Carboxylic Acid Encoded Glycopeptide Libraries , 1998 .

[76]  P. Keifer Influence of Resin Structure, Tether Length, and Solvent upon the High-Resolution (1)H NMR Spectra of Solid-Phase-Synthesis Resins. , 1996, The Journal of organic chemistry.

[77]  F. Lombardo,et al.  Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. , 2001, Advanced drug delivery reviews.

[78]  R. Carr,et al.  A photolabile carbamate based dual linker analytical construct for facile monitoring of solid phase chemistry: ‘TLC’ for solid phase? , 1999 .

[79]  Dimitris K. Agrafiotis,et al.  Stochastic Algorithms for Maximizing Molecular Diversity , 1997, J. Chem. Inf. Comput. Sci..

[80]  C. Wermuth,et al.  Glossary of terms used in medicinal chemistry (IUPAC Recommendations 1998) , 1998 .

[81]  L. Weber,et al.  Applications of genetic algorithms in molecular diversity. , 1998, Current opinion in chemical biology.

[82]  M. Bradley,et al.  Solid-Phase Dendrimer Synthesis and the Generation of Super-High-Loading Resin Beads for Combinatorial Chemistry , 1997 .

[83]  R. Houghten,et al.  Generation and use of synthetic peptide combinatorial libraries for basic research and drug discovery , 1991, Nature.

[84]  K. Nicolaou,et al.  Radiofrequency Encoded Combinatorial Chemistry , 1995 .

[85]  Kit S. Lam,et al.  The "One-Bead-One-Compound" Combinatorial Library Method. , 1997, Chemical reviews.

[86]  Peter Willett,et al.  Similarity Searching and Clustering of Chemical-Structure Databases Using Molecular Property Data , 1994, J. Chem. Inf. Comput. Sci..

[87]  S. P. Fodor,et al.  Light-directed, spatially addressable parallel chemical synthesis. , 1991, Science.

[88]  M. Lebl,et al.  Safety‐catch and multiply cleavable linkers in solid‐phase synthesis , 1999 .

[89]  Á. Furka Sub‐library composition of peptide libraries: Potential application in screening , 1994 .

[90]  Christine A. Miller,et al.  Improved Methods for Encoding and Decoding Dialkylamine-Encoded Combinatorial Libraries , 1999 .

[91]  R. Devraj,et al.  Chemical Library Purification Strategies Based on Principles of Complementary Molecular Reactivity and Molecular Recognition , 1997 .

[92]  Alan Dove,et al.  Drug screening—beyond the bottleneck , 1999, Nature Biotechnology.

[93]  B. J. Backes,et al.  Activation Method to Prepare a Highly Reactive Acylsulfonamide “Safety-Catch” Linker for Solid-Phase Synthesis1 , 1996 .

[94]  Hird Automated synthesis: new tools for the organic chemist. , 1999, Drug discovery today.

[95]  R A Houghten,et al.  "Libraries from libraries": chemical transformation of combinatorial libraries to extend the range and repertoire of chemical diversity. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[96]  K. Janda,et al.  Organic Synthesis on Soluble Polymer Supports: Liquid‐Phase Methodologies , 1997 .

[97]  V. Krchnak,et al.  Multiple release of equimolar amounts of peptides from a polymeric carrier using orthogonal linkage-cleavage chemistry. , 2009, International journal of peptide and protein research.

[98]  J. C. Hodges,et al.  Polymer-Supported Quenching Reagents for Parallel Purification , 1997 .

[99]  S. S. Wang p-alkoxybenzyl alcohol resin and p-alkoxybenzyloxycarbonylhydrazide resin for solid phase synthesis of protected peptide fragments. , 1973, Journal of the American Chemical Society.

[100]  L. Xue,et al.  Identification of a Preferred Set of Molecular Descriptors for Compound Classification Based on Principal Component Analysis. , 1999 .

[101]  H. M. Geysen,et al.  Isotope or mass encoding of combinatorial libraries. , 1996, Chemistry & biology.

[102]  Arasu Ganesan,et al.  Strategies for the Dynamic Integration of Combinatorial Synthesis and Screening. , 1998, Angewandte Chemie.

[103]  Chanfeng Zhao,et al.  Combinatorial Chemistry with Laser Optical Encoding , 1997 .

[104]  Malcolm J. McGregor,et al.  Pharmacophore Fingerprinting. 1. Application to QSAR and Focused Library Design , 1999, J. Chem. Inf. Comput. Sci..

[105]  R. B. Merrifield,et al.  Quantitative monitoring of solid-phase peptide synthesis by the ninhydrin reaction. , 1981, Analytical biochemistry.