Sherin S. Abdel-Meguid
- Published in print:
- 2007
- Published Online:
- September 2007
- ISBN:
- 9780198520979
- eISBN:
- 9780191706295
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780198520979.003.0017
- Subject:
- Biology, Biochemistry / Molecular Biology
This chapter discusses macromolecular crystallography in drug discovery. Currently, all large and most small pharmaceutical and biotechnology companies have invested in macromolecular ...
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This chapter discusses macromolecular crystallography in drug discovery. Currently, all large and most small pharmaceutical and biotechnology companies have invested in macromolecular crystallography, with protein crystallography now an integral tool of drug discovery. During the last twenty years, the term rational drug design has slowly been replaced with the more precise term structure-based drug design (SBDD).Less
This chapter discusses macromolecular crystallography in drug discovery. Currently, all large and most small pharmaceutical and biotechnology companies have invested in macromolecular crystallography, with protein crystallography now an integral tool of drug discovery. During the last twenty years, the term rational drug design has slowly been replaced with the more precise term structure-based drug design (SBDD).
Mark R. Sanderson and Jane V. Skelly (eds)
- Published in print:
- 2007
- Published Online:
- September 2007
- ISBN:
- 9780198520979
- eISBN:
- 9780191706295
- Item type:
- book
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780198520979.001.0001
- Subject:
- Biology, Biochemistry / Molecular Biology
Macromolecular crystallography is the study of macromolecules (proteins and nucleic acids) using X-ray crystallographic techniques in order to determine their molecular structure. The knowledge of ...
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Macromolecular crystallography is the study of macromolecules (proteins and nucleic acids) using X-ray crystallographic techniques in order to determine their molecular structure. The knowledge of accurate molecular structures is a pre-requisite for rational drug design, and for structure-based function studies to aid the development of effective therapeutic agents and drugs. The successful determination of the complete genome (genetic sequence) of several species (including humans) has recently directed scientific attention towards identifying the structure and function of the complete complement of proteins that make up that species; a new and rapidly growing field of study called ‘structural genomics’. There are now several important and well-funded global initiatives in operation to identify all of the proteins of key model species. One of the main requirements for these initiatives is a high-throughput crystallization facility to speed-up the protein identification process. The extent to which these technologies have advanced calls for an updated review of current crystallographic theory and practice. This book features the latest conventional and high-throughput methods, and includes contributions from a team of internationally recognized leaders and experts.Less
Macromolecular crystallography is the study of macromolecules (proteins and nucleic acids) using X-ray crystallographic techniques in order to determine their molecular structure. The knowledge of accurate molecular structures is a pre-requisite for rational drug design, and for structure-based function studies to aid the development of effective therapeutic agents and drugs. The successful determination of the complete genome (genetic sequence) of several species (including humans) has recently directed scientific attention towards identifying the structure and function of the complete complement of proteins that make up that species; a new and rapidly growing field of study called ‘structural genomics’. There are now several important and well-funded global initiatives in operation to identify all of the proteins of key model species. One of the main requirements for these initiatives is a high-throughput crystallization facility to speed-up the protein identification process. The extent to which these technologies have advanced calls for an updated review of current crystallographic theory and practice. This book features the latest conventional and high-throughput methods, and includes contributions from a team of internationally recognized leaders and experts.
GAUTAM R. DESIRAJU and THOMAS STEINER
- Published in print:
- 2001
- Published Online:
- January 2010
- ISBN:
- 9780198509707
- eISBN:
- 9780191708206
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780198509707.003.0004
- Subject:
- Physics, Crystallography
This chapter reviews the weak hydrogen bond in supramolecular chemistry by focusing on the relevance of these interactions in the analysis, design, and synthesis of the structures of molecular ...
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This chapter reviews the weak hydrogen bond in supramolecular chemistry by focusing on the relevance of these interactions in the analysis, design, and synthesis of the structures of molecular assemblies, most notably crystals. Supramolecular chemistry signifies chemistry beyond the molecule and deals with implications of the fact that molecules can recognise one another via intermolecular interactions, typically in condensed media. This field has grown into two distinct branches: the study of supermolecules in solution and in the solid state, mainly in crystal structures. The most important distinction between these two situations is not structural but lies in the lifetime of the interactions − supramolecular association in the crystal is time-stable whereas in solution it is not. The present chapter mainly concentrates on solid-state supramolecular systems, and discusses the role of weak hydrogen bonds in inclusion complexes such as crown ethers, oligoaryl hosts, and cyclodextrins (cycloamyloses). The promises and problems of crystal engineering are also considered, together with drug design and biological recognition.Less
This chapter reviews the weak hydrogen bond in supramolecular chemistry by focusing on the relevance of these interactions in the analysis, design, and synthesis of the structures of molecular assemblies, most notably crystals. Supramolecular chemistry signifies chemistry beyond the molecule and deals with implications of the fact that molecules can recognise one another via intermolecular interactions, typically in condensed media. This field has grown into two distinct branches: the study of supermolecules in solution and in the solid state, mainly in crystal structures. The most important distinction between these two situations is not structural but lies in the lifetime of the interactions − supramolecular association in the crystal is time-stable whereas in solution it is not. The present chapter mainly concentrates on solid-state supramolecular systems, and discusses the role of weak hydrogen bonds in inclusion complexes such as crown ethers, oligoaryl hosts, and cyclodextrins (cycloamyloses). The promises and problems of crystal engineering are also considered, together with drug design and biological recognition.
Brent R. Stockwell
- Published in print:
- 2013
- Published Online:
- November 2015
- ISBN:
- 9780231152136
- eISBN:
- 9780231525527
- Item type:
- chapter
- Publisher:
- Columbia University Press
- DOI:
- 10.7312/columbia/9780231152136.003.0002
- Subject:
- Public Health and Epidemiology, Public Health
This chapter explains how small molecules came to be used as drugs and how they function mechanistically. It begins by focusing on the emergence of organic chemistry and the role played by Justus von ...
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This chapter explains how small molecules came to be used as drugs and how they function mechanistically. It begins by focusing on the emergence of organic chemistry and the role played by Justus von Liebig in the birth of organic chemistry through the isolation and synthesis of highly purified small molecules, paying special attention to his pioneering studies on fulminic acid and his collaboration with Friedrich Wohler that led to their discovery of the first example of isomers. The chapter then considers two related approaches for generating biologically active molecules: synthesis and extraction, along with Wohler’s synthesis of urea in 1828. It also discusses advances in extraction methods for purifying molecules from natural sources; the combination of extraction and synthesis methods to make derivatives of molecules found in nature, including the discovery of fever-reducing drugs; changes in the approach to drug discovery that laid the foundation for defining the problem of the undruggable proteins; the emergence of molecular medicine; and the rise of structure-based drug design.Less
This chapter explains how small molecules came to be used as drugs and how they function mechanistically. It begins by focusing on the emergence of organic chemistry and the role played by Justus von Liebig in the birth of organic chemistry through the isolation and synthesis of highly purified small molecules, paying special attention to his pioneering studies on fulminic acid and his collaboration with Friedrich Wohler that led to their discovery of the first example of isomers. The chapter then considers two related approaches for generating biologically active molecules: synthesis and extraction, along with Wohler’s synthesis of urea in 1828. It also discusses advances in extraction methods for purifying molecules from natural sources; the combination of extraction and synthesis methods to make derivatives of molecules found in nature, including the discovery of fever-reducing drugs; changes in the approach to drug discovery that laid the foundation for defining the problem of the undruggable proteins; the emergence of molecular medicine; and the rise of structure-based drug design.
Brent Stockwell
- Published in print:
- 2013
- Published Online:
- November 2015
- ISBN:
- 9780231152136
- eISBN:
- 9780231525527
- Item type:
- book
- Publisher:
- Columbia University Press
- DOI:
- 10.7312/columbia/9780231152136.001.0001
- Subject:
- Public Health and Epidemiology, Public Health
After more than fifty years of blockbuster drug development, skeptics are beginning to fear we are reaching the end of drug discovery to combat major diseases. This book describes this dilemma and ...
More
After more than fifty years of blockbuster drug development, skeptics are beginning to fear we are reaching the end of drug discovery to combat major diseases. This book describes this dilemma and the powerful techniques that may bring drug research into the twenty-first century. Filled with absorbing stories of breakthroughs, this book begins with the scientific achievements of the twentieth century that led to today’s drug innovations. We learn how the invention of mustard gas in World War I led to early anti-cancer agents and how the efforts to decode the human genome might lead to new approaches in drug design. The book then turns to the seemingly incurable diseases we face today, such as Alzheimer’s, many cancers, and others with no truly effective medicines, and details the cellular and molecular barriers thwarting scientists equipped with only the tools of traditional pharmaceutical research. Scientists are now developing methods to combat these complexities—technologies for constructing and testing millions of drug candidates, sophisticated computational modeling, and entirely new classes of drug molecules—all with an eye toward solving the most profound mysteries of living systems and finding cures for intractable diseases. If successful, these methods will unlock a vast terrain of untapped drug targets that could lead to a bounty of breakthrough medicines.Less
After more than fifty years of blockbuster drug development, skeptics are beginning to fear we are reaching the end of drug discovery to combat major diseases. This book describes this dilemma and the powerful techniques that may bring drug research into the twenty-first century. Filled with absorbing stories of breakthroughs, this book begins with the scientific achievements of the twentieth century that led to today’s drug innovations. We learn how the invention of mustard gas in World War I led to early anti-cancer agents and how the efforts to decode the human genome might lead to new approaches in drug design. The book then turns to the seemingly incurable diseases we face today, such as Alzheimer’s, many cancers, and others with no truly effective medicines, and details the cellular and molecular barriers thwarting scientists equipped with only the tools of traditional pharmaceutical research. Scientists are now developing methods to combat these complexities—technologies for constructing and testing millions of drug candidates, sophisticated computational modeling, and entirely new classes of drug molecules—all with an eye toward solving the most profound mysteries of living systems and finding cures for intractable diseases. If successful, these methods will unlock a vast terrain of untapped drug targets that could lead to a bounty of breakthrough medicines.
