Interactions Between Small Molecule Ligands and Target Enzymes PDF Download

Author: Sung-Kun (Sean) Kim
Publisher: Frontiers Media SA
ISBN: 2889666859
Category : Science
Languages : en
Pages : 120

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Author: Hans-Joachim Böhm
Publisher: John Wiley & Sons
ISBN: 3527605517
Category : Science
Languages : en
Pages : 262

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Book Description
The lock-and-key principle formulated by Emil Fischer as early as the end of the 19th century has still not lost any of its significance for the life sciences. The basic aspects of ligand-protein interaction may be summarized under the term 'molecular recognition' and concern the specificity as well as stability of ligand binding. Molecular recognition is thus a central topic in the development of active substances, since stability and specificity determine whether a substance can be used as a drug. Nowadays, computer-aided prediction and intelligent molecular design make a large contribution to the constant search for, e. g., improved enzyme inhibitors, and new concepts such as that of pharmacophores are being developed. An up-to-date presentation of an eternally young topic, this book is an indispensable information source for chemists, biochemists and pharmacologists dealing with the binding of ligands to proteins.

Author: Herbert Waldmann
Publisher: Springer Science & Business Media
ISBN: 9783540439844
Category : Medical
Languages : en
Pages : 248

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Book Description
Based on the international workshop on 'Small Molecule - Protein Interactions' held in Berlin, April 24-26, 2002, researchers from industry and academic laboratories describe novel and efficient ways selecting promising new drug targets and developing small molecule inhibitors against them. The structure of the book corresponds to the different aspects of the drug discovery process. All chapters are written by leading experts in the field, who present and discuss the most recent state-of-the-art tools and techniques for the development of novel drugs. The value of the book lies in surveying and summarizing the approaches taken by different companies and institutions giving the reader a balanced view on the use of the latest techniques on the one hand and experience-based assistance in selecting appropriate tools for their own work on the other hand.

Author: Alberto Diaspro
Publisher: CRC Press
ISBN: 1420078895
Category : Science
Languages : en
Pages : 450

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"Alberto Diaspro has been choreographing light's dance for over 20 years, and in Nanoscopy and Multidimensional Optical Fluorescence Microscopy, he has assembled a diverse group of experts to explain the methods they use to coax light to reveal biology's secrets."- From the Foreword by Daniel Evanko, editor, Nature Methods Nanoscopy and Multidimens

Author: Samson Aeloa Souza
Publisher:
ISBN:
Category :
Languages : en
Pages :

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A druggable protein target is one in which an exogenous ligand will induce the desired response. In this work, small molecule interactions of three druggable protein targets will be detailed. The first of these is a bacterial enzyme involved in the synthesis of cofactor biotin, which is an essential cofactor exploited across all life domains. It is necessary for fatty acid biosynthesis, gluconeogenesis, and amino acid metabolism. Mammals lack the biosynthetic machinery to produce it and must acquire it in the diet. Meanwhile, bacteria such as E. coli, and M. tuberculosis can synthesize it endogenously. As such, enzymes involved in biotin synthesis are attractive targets in antimicrobial development. Diaminopelargonic acid synthase (BioA) catalyzes the second step in the conserved pathway from starting compounds pimeloyl-CoA and L-alanine. Unlike other bacteria, Bacillus subtilis requires L-lysine as a substrate for transamination of 7-keto-8-aminopelargonic acid (KAPA) to its diamino-product, 7,8-diaminopelargonic acid (DAPA), by BioA. I present kinetic work that suggests a donation of lysine [epsilon]-amino group to KAPA. I follow this with the crystal structure of PLP-conjugated lysine as an external aldimine (LLP). The adduct is stabilized by electrostatic interactions between the carboxylate and R410, and pi-cation interactions between the former lys [alpha]-amine and two aromatic side chains in the pocket. In the latter segment of this work, I survey ligand interactions of two membrane proteins directly involved in estrogen signaling. The first of these two proteins, G-protein coupled estrogen receptor (GPER), is localized in the endoplasmic reticulum. This research, which was the first to demonstrate in vitro ligand binding with recombinant protein, focuses on steps to produce functional GPER for structural and binding assays. GPER is a potential non-nuclear strategy for breast cancer therapy since 10 - 20 % of diagnoses are estrogen receptor negative. The second estrogen-related protein I will explore is the cytochrome P450 enzyme aromatase (Cyp19). It catalyzes the last biosynthetic step in the production of endogenous estrogens in mammals. To this end, it is a current target in the treatment of hormone-related illnesses and diseases such as endometriosis, ovarian cancer, and breast cancer. Current aromatase inhibitors (AIs), for instance, tamoxifen, are potent, yet they often lead to debilitating side effects. Eventual relapse creates a need for novel breast cancer therapeutics that improve patient outcome. Virtual screening of a library of millions of compounds is often employed to initially uncover drug candidates. I provide activity data of these top hit candidates against a putative Cyp19 allosteric site. Two lead compounds, AR11 and AR13, exhibit potent, anti-aromatase activity comparable to active tamoxifen metabolite, endoxifen. Inhibitory mechanisms of these compounds and the journey to find a promising construct for cocrystallization will be explored. This insight will aid in the search to unearth a novel class of allosteric aromatase inhibitors with diverse toxicity profiles.

Author: Flavio Ballante
Publisher: Humana
ISBN: 9781071612088
Category : Medical
Languages : en
Pages : 327

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Book Description
This detailed book collects modern and established computer-based methods aimed at addressing the drug discovery challenge from disparate perspectives by exploiting information on ligand-protein recognition. Beginning with methods that allow for the exploration of specific areas of chemical space and the designing of virtual libraries, the volume continues with sections on methods based on docking, quantitative models, and molecular dynamics simulations, which are employed for ligand discovery or development, as well as methods exploiting an ensemble of protein structures for the identification of potential protein targets. Written for the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Protein-Ligand Interactions and Drug Design provides detailed practical procedures of solid computer-aided drug design methodologies employed to rationalize and optimize protein-ligand interactions, for experienced researchers and novices alike.

Author: Wolfgang Jahnke
Publisher: John Wiley & Sons
ISBN: 3527608605
Category : Science
Languages : en
Pages : 391

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Book Description
This first systematic summary of the impact of fragment-based approaches on the drug development process provides essential information that was previously unavailable. Adopting a practice-oriented approach, this represents a book by professionals for professionals, tailor-made for drug developers in the pharma and biotech sector who need to keep up-to-date on the latest technologies and strategies in pharmaceutical ligand design. The book is clearly divided into three sections on ligand design, spectroscopic techniques, and screening and drug discovery, backed by numerous case studies.

Author: Ana Cecília A. Roque
Publisher: Methods in Molecular Biology
ISBN:
Category : Medical
Languages : en
Pages : 316

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Book Description
In this authoritative book, experts in the field highlight the main principles and methodologies currently utilized in the study of molecular interactions between compounds. This is as an ideal guide to those striving to further our knowledge of medicines.

Author: Kristina Elisabet Furse
Publisher:
ISBN:
Category : Cyclooxygenases
Languages : en
Pages : 366

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Author: Jean-Paul Renaud
Publisher: John Wiley & Sons
ISBN: 1118900502
Category : Medical
Languages : en
Pages : 1367

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Book Description
With the most comprehensive and up-to-date overview of structure-based drug discovery covering both experimental and computational approaches, Structural Biology in Drug Discovery: Methods, Techniques, and Practices describes principles, methods, applications, and emerging paradigms of structural biology as a tool for more efficient drug development. Coverage includes successful examples, academic and industry insights, novel concepts, and advances in a rapidly evolving field. The combined chapters, by authors writing from the frontlines of structural biology and drug discovery, give readers a valuable reference and resource that: Presents the benefits, limitations, and potentiality of major techniques in the field such as X-ray crystallography, NMR, neutron crystallography, cryo-EM, mass spectrometry and other biophysical techniques, and computational structural biology Includes detailed chapters on druggability, allostery, complementary use of thermodynamic and kinetic information, and powerful approaches such as structural chemogenomics and fragment-based drug design Emphasizes the need for the in-depth biophysical characterization of protein targets as well as of therapeutic proteins, and for a thorough quality assessment of experimental structures Illustrates advances in the field of established therapeutic targets like kinases, serine proteinases, GPCRs, and epigenetic proteins, and of more challenging ones like protein-protein interactions and intrinsically disordered proteins