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Barry A. Bunin

Bio: Barry A. Bunin is an academic researcher from Collaborative Drug Discovery. The author has contributed to research in topics: Solid-phase synthesis & Cheminformatics. The author has an hindex of 21, co-authored 46 publications receiving 2078 citations. Previous affiliations of Barry A. Bunin include University of California, Berkeley.

Papers
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Journal ArticleDOI
TL;DR: A library of 192 structurally diverse 1,4-benzodiazepine derivatives containing a variety of chemical functionalities including amides, carboxylic acids, amines, phenols, and indoles was constructed from three components, 2-aminobenzophenones, amino acids, and alkylating agents, by employing Geysen's pin apparatus.
Abstract: A library of 192 structurally diverse 1,4-benzodiazepine derivatives containing a variety of chemical functionalities including amides, carboxylic acids, amines, phenols, and indoles was constructed from three components, 2-aminobenzophenones, amino acids, and alkylating agents, by employing Geysen's pin apparatus [Geysen, H. M., Rodda, S. J., Mason, T. J., Tribbick, G. & Schoofs, P. G. (1987) J. Immunol. Methods 102, 259-274]. Rigorous analytical verification of the chemical integrity and yield of a representative collection of the diverse derivatives was carried out. In addition, the library of derivatives was evaluated for binding to the cholecystokinin A receptor by employing a competitive radio-ligand binding assay. This provided detailed structure versus activity relationships that were confirmed by independent large-scale synthesis and evaluation of several of the 1,4-benzodiazepine derivatives.

323 citations

Book
03 Mar 1998
TL;DR: A summary of functional group transformations for Combinatorial solid phase synthesis can be found in this paper, along with a list of abbreviations and a discussion of analytical methods for synthesizing Oligosaccharides.
Abstract: Introduction. Background. Linkers for Solid-Phase Synthesis. Combinatorial Solid-Phase Synthesis. Analytical Methods for Solid-Phase Synthesis. The Preparation of Solution Libraries and Combined Approaches at the Solution/Solid-Phase Interface. Appendix 1: Summary of Functional Group Transformations for Combinatorial Solid-Phase Synthesis. Appendix 2: Classification of Heterocyclization Reactions. Appendix 3: Unnatural Biopolymers. Appendix 4: Oligosaccharides. Appendix 5:List of Abbreviations. Index.

182 citations

Journal ArticleDOI
TL;DR: This work argues that a community-based platform that combines traditional drug discovery informatics with Web2.0 features in secure groups is believed to be the key to facilitating richer, instantaneous collaborations involving sensitive drug discovery data and intellectual property.

133 citations

Patent
02 Mar 2012
TL;DR: In this paper, the peptide-based compounds including heteroatom-containing, three-membered rings efficiently and selectively inhibit specific activities of N-terminal nucleophile (Ntn) hydrolases.
Abstract: Peptide-based compounds including heteroatom-containing, three-membered rings efficiently and selectively inhibit specific activities of N-terminal nucleophile (Ntn) hydrolases. The activities of those Ntn having multiple activities can be differentially inhibited by the compounds described. For example, the chymotrypsin-like activity of the 20S proteasome may be selectively inhibited with the inventive compounds. The peptide-based compounds include at least three peptide units, an epoxide or aziridine, and functionalization at the N-terminus. Among other therapeutic utilities, the peptide-based compounds are expected to display anti-inflammatory properties and inhibition of cell proliferation.

109 citations


Cited by
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Journal ArticleDOI
TL;DR: Privileged substructures are believed to achieve this through the mimicry of common protein surface elements that are responsible for binding, such as β- and gamma;-turns.
Abstract: Privileged substructures are of potentially great importance in medicinal chemistry. These scaffolds are characterized by their ability to promiscuously bind to a multitude of receptors through a variety of favorable characteristics. This may include presentation of their substituents in a spatially defined manner and perhaps also the ability to directly bind to the receptor itself, as well as exhibiting promising characteristics to aid bioavailability of the overall molecule. It is believed that some privileged substructures achieve this through the mimicry of common protein surface elements that are responsible for binding, such as β- and gamma;-turns. As a result, these structures represent a promising means by which new lead compounds may be identified.

2,620 citations

Journal ArticleDOI
17 Mar 2000-Science
TL;DR: Several synthetic planning principles for diversity-oriented synthesis and their role in the drug discovery process are presented in this review.
Abstract: Modern drug discovery often involves screening small molecules for their ability to bind to a preselected protein target. Target-oriented syntheses of these small molecules, individually or as collections (focused libraries), can be planned effectively with retrosynthetic analysis. Drug discovery can also involve screening small molecules for their ability to modulate a biological pathway in cells or organisms, without regard for any particular protein target. This process is likely to benefit in the future from an evolving forward analysis of synthetic pathways, used in diversity-oriented synthesis, that leads to structurally complex and diverse small molecules. One goal of diversity-oriented syntheses is to synthesize efficiently a collection of small molecules capable of perturbing any disease-related biological pathway, leading eventually to the identification of therapeutic protein targets capable of being modulated by small molecules. Several synthetic planning principles for diversity-oriented synthesis and their role in the drug discovery process are presented in this review.

2,229 citations

Journal ArticleDOI
TL;DR: In this article, the authors propose a method to solve the problem of "uniformity" in the literature: 1.0040−4020/$ doi:10.1016/

1,581 citations

Journal ArticleDOI
TL;DR: Thompson et al. as mentioned in this paper developed a method for the generation of large combinatorial libraries of peptides and oligonucleotides that are then screened against a receptor or enzyme to identify high affinity ligands or potent inhibitors, respectively.
Abstract: One of the initial steps in the development of therapeutic agents is the identification of lead compounds that bind to the receptor or enzyme target of interest. Many analogs of these lead compounds are then synthesized to define the key recognition elements for maximal activity. In general, many compounds must be evaluated in both the lead identification and optimization steps. Increasing burdens have been placed on these efforts due to the large number of new therapeutic targets that continue to be identified thorough modern molecular biology methods.1 To address this demand, very powerful chemical and biological methods have been developed for the generation of large combinatorial libraries of peptides2 and oligonucleotides3 that are then screened against a receptor or enzyme to identify high-affinity ligands or potent inhibitors, respectively. While these studies have clearly demonstrated the power of library synthesis and screening strategies, peptides and oligonucleotides generally have poor oral activities and rapid in vivo clearance;4 therefore their utility as bioavailable therapeutic agents is often limited. Due to the favorable pharmacokinetic properties of many small organic molecules (<600-700 molecular weight),5 the design, synthesis, and evaluation of libraries of these compounds6 has rapidly become a major frontier in organic chemistry. Lorin A. Thompson was born in Lexington, KY, in 1970. He received the Bachelor of Science degree from the University of North Carolina, Chapel Hill, in 1992 where he worked under the guidance of Joseph Desimone. He is currently pursuing his doctorate in the laboratory of Jonathan Ellman at UC Berkeley where he is the 1994 Glaxo-Wellcome fellow. His research interests include the development of synthetic methodology for organic library construction.

1,440 citations

Journal ArticleDOI
TL;DR: This review explores the concept of using privileged scaffolds to identify biologically active compounds through building chemical libraries by revealing through four selected examples the present state of the art in privileged scaffold library synthesis.

1,160 citations