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|z 9780443158711
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|a RM301.25
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|a 615.19
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| 245 |
0 |
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|a Modern methods of drug design and development /
|c edited by Matthew Lloyd.
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| 250 |
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|a 1st ed.
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| 264 |
|
1 |
|a San Diego :
|b Elsevier Science & Technology,
|c 2023.
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| 264 |
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4 |
|c �2023
|
| 300 |
|
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|a 1 online resource (xxiv, 574 pages).
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| 336 |
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|a text
|b txt
|2 rdacontent
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|a computer
|b c
|2 rdamedia
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|a online resource
|b cr
|2 rdacarrier
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| 490 |
1 |
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|a Methods in enzymology ;
|v volume six hundred and ninety
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| 588 |
|
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|a Description based on publisher supplied metadata and other sources.
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| 505 |
8 |
|
|a Chapter Two: Steady-state kinetic analysis of reversible enzyme inhibitors: A case study on calf intestine alkaline phosphatase -- 1 Introduction -- 2 Measurements of 4-nitrophenol pKa -- 2.1 Key resources table -- 2.2 Materials and equipment -- 2.2.1 Alternatives -- 2.3 Step-by-step method details -- 2.3.1 Making the series of buffers -- 2.3.1.1 Timing: Day 1 -- 2.3.2 Measuring the 4-nitrophenol pKa value -- 2.3.2.1 Timing: Day 1 or 2 -- 2.3.3 Data analysis -- 2.3.3.1 Timing: Day 1 or 2 -- 2.4 Expected outcomes, advantages and limitations -- 2.5 Statistical analysis -- 2.6 Optimization and troubleshooting -- 2.7 Safety considerations and standards -- 3 Alkaline phosphatase assays -- 3.1 Key resources table -- 3.2 Materials and equipment -- 3.2.1 Alternatives -- 3.3 Step-by-step method details -- 3.3.1 Determining the amount of enzyme required in the assay -- 3.3.2 Calculation of adjusted 4-nitrophenol extinction coefficient -- 3.3.3 Calculation of reaction rates -- 3.3.4 Determining the effect of additives on the enzyme activity -- 3.3.5 Determining kinetic parameters for alkaline phosphatase -- 3.3.6 Determination of Km and Vmax values using the direct linear plot -- 3.3.7 Determination of Km and Vmax values using the enzyme kinetics macro -- 3.3.8 Calculation of numerical values for kinetic parameters -- 3.3.9 Measurement of Z2 -- 3.3.10 Dose-response curves and determination of pIC50 values -- 3.3.10.1 Data collection -- 3.3.11 Data processing and determination of pIC50 values -- 3.3.12 Rapid dilution experiment to determine inhibitor reversibility -- 3.3.12.1 Collection of data -- 3.3.13 Data processing -- 3.3.14 Determination of Ki values -- 3.3.15 Collection of data -- 3.3.16 Data processing -- 3.3.17 Determining the type of inhibition -- 3.3.18 Statistical analysis of the results and determination of significance.
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| 505 |
8 |
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|a 3.4 Expected outcomes, advantages and limitations -- 3.5 Statistical analysis -- 3.6 Optimization and troubleshooting -- 3.7 Safety considerations and standards -- Acknowledgments -- References -- Chapter Three: Non-equilibrium modalities of inhibition: Characterizing irreversible inhibition for the ErbB receptor family membersHigh-throughput experimentation and analysis of irreversible inhibition -- 1 Introduction -- 1.1 Life as a kinetic state of matter -- 1.2 Brief theory of slow binding and irreversible inhibition -- 2 Protocol -- 2.1 Key resource table -- 2.2 Materials and equipment employed in this study -- 2.3 Step-by-step method details -- 2.3.1 Making the buffers, substrate and enzyme -- 2.3.2 Step by step guide on how to run the assay -- 2.3.3 Data analysis -- 2.3.4 Considerations when interpreting assay results -- 2.4 Optimization and troubleshooting -- 2.5 Statistical analysis -- 2.6 Safety considerations and standards -- Acknowledgements -- Declaration of conflicting interests -- Data and software availability -- Funding -- References -- Chapter Four: Analysis of continuous enzyme kinetic data using ICEKAT -- 1 Introduction -- 2 Program implementation -- 3 User's guide to ICEKAT -- 3.1 Required materials -- 3.2 Continuous enzyme kinetic assay data analysis in ICEKAT -- 3.2.1 Preparing and uploading data to ICEKAT -- 3.2.2 Semi-automated ICEKAT data analysis -- 3.3 Special considerations for specific ICEKAT analysis models -- 3.3.1 pEC50/pIC50 model -- 3.3.2 HTS model -- 3.4 Special considerations for specific ICEKAT analysis modes -- 3.4.1 Schnell-Mendoza mode -- 3.4.2 Logarithmic Fit mode -- 4 Data processing -- 5 Expected outcomes, advantages, and limitations -- 6 Conclusions -- Acknowledgments -- References.
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| 505 |
8 |
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|a 3.3.1.3 General Method C: Evan's auxiliary cleavage -- 3.3.1.4 General Method D: Synthesis of acyl-CoA esters -- 3.3.2 Synthesis of S-2-[13C]-2-[2H]-2-methyldecanoyl-CoA 10 -- 3.3.2.1 Synthesis of ethyl [2-13C]-2-ethoxycarbonyldecanoate 12 -- 3.3.2.2 Synthesis of 2-[13C]-2-[2H2]-decanoic acid 13 -- 3.3.3 Synthesis of Anti-(2R,3R)-3-fluoro-2-methyldecanoyl-CoA (17) -- 3.3.3.1 Synthesis of (R)-4-benzyl-3-propanoyloxazolidin-2-one 19 -- 3.3.3.2 Synthesis of (R)-4-benzyl-3-[(2R,3S)-3-hydroxy-2-methyldecanoyl]oxazolidin-2-one 20 -- 3.3.3.3 Synthesis of (R)-4-benzyl-3-[(2S,3R)-3-fluoro-2-methyldecanoyl]oxazolidin-2-one 21 -- 3.3.3.4 Synthesis of (2S,3R)-3-fluoro-2-methyldecanoic acid 22 -- 3.3.3.5 Synthesis of (2R,3R)-3-fluoro-2-methyldecanoyl-CoA 17 -- 3.3.4 Synthesis of colorimetric substrate 23 -- 3.3.4.1 Synthesis of 2R,S-3-(2,4-dinitrophenoxy)-2-methylpropan-1-ol 26 -- 3.3.4.2 Synthesis of 2R,S-3-(2,4-dinitrophenoxy)-2-methylpropanoic acid 27 -- 3.3.4.3 Synthesis of 2R,S-3-(2,4-dinitrophenoxy)-2-methylpropanoyl-CoA 23 -- 3.4 Expected outcomes, advantages and limitations -- 3.4.1 Synthesis of precursor acids -- 3.4.2 Synthesis of acyl-CoA esters (General Method D) -- 3.5 Optimization and troubleshooting -- 3.6 Safety considerations and standards -- 4 NMR assays of recombinant human AMACR 1A -- 4.1 Key resources table -- 4.2 Materials and equipment -- 4.3 Step-by-step method details -- 4.3.1 2H-exchange assay for acyl-CoA ester substrates -- 4.3.2 Analysis of the stereochemical outcome of the reaction of 2-methylacyl-CoA esters with AMACR -- 4.4 Expected outcomes, advantages and limitations -- 4.5 Quantification and data analysis methods -- 4.5.1 Data collection and referencing -- 4.5.2 Data processing -- 4.5.3 NMR assays with double labeled substrates -- 4.5.4 NMR assays with eliminating substrates -- 4.6 Optimization and troubleshooting -- 4.7 Safety considerations and standards.
|
| 650 |
|
0 |
|a Drug development
|x Methodology.
|
| 650 |
|
0 |
|a Drugs
|x Design
|x Methodology.
|
| 650 |
|
6 |
|a M�edicaments
|0 (CaQQLa)201-0306620
|x D�eveloppement
|0 (CaQQLa)201-0306620
|x M�ethodologie.
|0 (CaQQLa)201-0379663
|
| 650 |
|
6 |
|a M�edicaments
|0 (CaQQLa)201-0203461
|x Conception
|0 (CaQQLa)201-0203461
|x M�ethodologie.
|0 (CaQQLa)201-0379663
|
| 655 |
|
0 |
|a Electronic books.
|
| 700 |
1 |
|
|a Lloyd, Matthew,
|e editor.
|
| 776 |
0 |
8 |
|i Print version:
|a Lloyd, Matthew
|t Modern Methods of Drug Design and Development
|d San Diego : Elsevier Science & Technology,c2023
|z 9780443158711
|
| 830 |
|
0 |
|a Methods in enzymology ;
|v v. 690.
|
| 856 |
4 |
0 |
|u https://sciencedirect.uam.elogim.com/science/bookseries/00766879/690
|z Texto completo
|
| 880 |
8 |
|
|6 505-00/(S
|a Chapter Five: You get what you screen for: Standards for experimental design and data fitting in drug discoveryData fitting in drug discovery -- 1 An introduction to mechanism-based computer simulation and data fitting -- 2.1 Modeling steady-state kinetic data -- 2.2 Modeling competition -- 2.3 Kinetics of substrate binding: Confidence contour analysis -- 3 Modeling and fitting equilibrium binding data -- 3.1 Special syntax for entering a titration -- 3.2 Fitting dose-response curves -- 3.3 Time to reach equilibrium -- 3.4 Fitting dose/response curves using the Hill equation -- 3.5 Fitting cooperative binding -- 3.6 Asymmetry in titration curves -- 4 Signals for measuring equilibrium binding and kinetics -- 4.1 Fluorescence methods combining kinetic and equilibrium measurements -- 4.2 Alternative labeling methods -- 4.3 Modeling coupled reactions -- 5 Global data fitting -- 6 Summary -- Funding support/Acknowledgments -- Conflict of interest -- References -- Chapter Six: Analysis of enzyme reactions using NMR techniques: A case study with α-methylacyl-CoA racemase (AMACR) -- 1 Introduction -- 2 Purification of recombinant human AMACR 1A -- 2.1 Key resources table -- 2.2 Materials and equipment -- 2.3 Step-by-step method details -- 2.3.1 Transformation of plasmid and growth of recombinant E. coli cells -- 2.3.2 Purification of recombinant human AMACR using metal-chelate chromatography -- 2.4 Expected outcomes, advantages and limitations -- 2.5 Optimization and troubleshooting -- 2.6 Safety considerations and standards -- 3 Synthesis and quantification of acyl-CoA substrates -- 3.1 Key resources table -- 3.2 Materials and equipment -- 3.3 Step-by-step method details -- 3.3.1 General synthetic procedures -- 3.3.1.1 General Method A: Acid coupling to evans auxiliary -- 3.3.1.2 General Method B: Methylation.
|
| 880 |
0 |
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|6 505-00/(S
|a Front Cover -- Series Page -- Title Page -- Copyright -- Contents -- Contributors -- Preface -- References -- Chapter One: Recombinant protein production for structural and kinetic studies: A case study using M. tuberculosis α-methylacyl-CoA racemase (MCR) -- 1 Introduction -- 2 Recombinant protein production -- 2.1 Key resources table -- 2.2 Materials and equipment -- 2.2.1 Equipment -- 2.2.2 Solutions and consumables -- Alternatives -- 2.3 Step-by-step method details -- 2.3.1 Production of competent cells and plasmid transformation -- 2.3.2 Growth of E. coli starter cultures -- 2.3.3 Growth of E. coli cultures and production of recombinant protein -- 2.4 Expected outcomes, advantages and disadvantages -- 2.5 Optimization and troubleshooting -- 2.6 Safety considerations and standards -- 3 Recombinant protein purification -- 3.1 Key resources table -- 3.2 Materials and equipment -- 3.2.1 Equipment -- 3.2.2 Solutions and consumables -- 3.3 Step-by-step method details -- 3.3.1 Cell lysis and purification using DEAE-Sepharose -- 3.3.2 Purification of pooled DEAE-Sepharose fractions using RESOURCE-Q column -- 3.3.3 Purification of pooled RESOURCE-Q fractions using size-exclusion chromatography -- 3.3.4 Buffer-exchange of purified target protein -- 3.4 Expected outcomes, advantages and disadvantages -- 3.5 Optimization and troubleshooting -- 3.6 Safety considerations and standards -- 4 Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) -- 4.1 Key resources table -- 4.2 Materials and equipment -- 4.2.1 Equipment -- 4.2.2 Solutions and consumables -- 4.3 Step-by-step method details -- 4.4 Expected outcomes, advantages and disadvantages -- 4.5 Optimization and troubleshooting -- 4.6 Safety considerations and standards -- Acknowledgements -- Conflict of interest -- References.
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