The impact of biotechnology and molecular biology on the pharmaceutical industry

1992 ◽  
Vol 99 (1-2) ◽  
pp. 37-45
Author(s):  
A. N. Hobden ◽  
T. J. R. Harris
Keyword(s):  
Drug Discovery ◽  
Pharmaceutical Industry ◽  
Protein Function ◽  
High Throughput Screening ◽  
Mammalian Cells ◽  
Recombinant Dna ◽  
Hiv Protease ◽  
Baculovirus Infection ◽  
Recombinant Dna Techniques ◽  
The Impact

Synopsis:Biotechnology had its initial impact on the pharmaceutical industry well before the perceived time. The use of fermentation technology to produce antibiotics was a cornerstone for the development of the industry. This event was both before cloning (BC) and before DNA (rather than after DNA – AD). Even now the antibiotic market, which is worth over 10 billion U.S. dollars a year, is the most valuable segment of the total market, (c.200 billion dollars per year). Nevertheless the impact of biotechnology in drug discovery was until recently perceived solely to be the use of recombinant DNA techniques to produce therapeutic proteins and modified versions of them by protein engineering.There are several other places where genetic engineering is influencing drug discovery. The expression of recombinant proteins in surrogate systems (e.g. in E. coli, yeast or via baculovirus infection or in mammalian cells) provides materials for structure determination (e.g. HIV protease) and structure/function studies (e.g. various receptors). Recombinant DNA techniques are influencing assay technology by allowing access to proteins in sufficient quantity for high throughput screening.In addition, screening organisms can be constructed where a particular protein function can be measured in a microorganism by complementation or via reporter gene expression.Transgenic animals also illustrate the power of the technology for drug discovery. Not only will transgenic rats and mice be used as models of disease but also for efficacy and toxicological profiling. What is learned in transgenic rodents may well set the scene for somatic cell gene therapy in humans.

The Small Molecules of Life

2014 ◽  
Author(s):  
Eugene H. Cordes
Keyword(s):  
Cell Wall ◽  
Protein Structure ◽  
Drug Discovery ◽  
Nucleic Acids ◽  
Small Molecules ◽  
Protein Function ◽  
Mammalian Cells ◽  
Living Organism ◽  
Living Organisms ◽  
Life On Earth

All life on Earth is unified. Life may have flickered into being, only to be subsequently extinguished, many times during the early days of our planet’s evolution. But on exactly one occasion, life on Earth did arise and persist. Every living organism is a descendent of that life. We are all hatched from the same primeval egg. The universal roles of the big molecules of life—proteins and nucleic acids—reflect this unique origin. The genetic code that links the language of nucleic acids to that of proteins is universal throughout the amazing diversity of living organisms. Protein relatives serve the same or similar functions in living organisms from wheat to humans. We are going to have a closer look at the proteins as we move forward: protein structure in chapter 3, protein function in chapter 4, and proteins as targets for drug discovery in chapters 6 through 12. This is not to argue that there are no differences among the molecules of life. Clearly, there are. For example, bacteria are isolated from their environment by a surrounding cell wall. There is no related structure in mammalian cells. We take advantage of these differences to sustain and restore human health. For example, many antibiotics act by preventing construction of bacterial cell walls. We will see two examples in what follows: Primaxin and fludalanine. The unity of life extends to the small molecules of life as well. There is compelling similarity among the small molecules that carry out critical functions of life. Adenosine triphosphate (ATP) is the universal energy currency of life; molecules that transmit messages from one nerve cell to another are shared between sea snails and humans. Molecules on the routes of metabolic pathways are much the same in fruit flies and flying bats, and on and on.

The impact of chemoinformatics on drug discovery in the pharmaceutical industry

2020 ◽  
Vol 15 (3) ◽  
pp. 293-306 ◽  
Author(s):  
Karina Martinez-Mayorga ◽  
Abraham Madariaga-Mazon ◽  
José L. Medina-Franco ◽  
Gerald Maggiora
Keyword(s):  
Drug Discovery ◽  
Pharmaceutical Industry ◽  
The Impact

scholarly journals Evolution of the SARS-CoV-2 proteome in three dimensions (3D) during the first six months of the COVID-19 pandemic

2020 ◽  
Author(s):  
Joseph H. Lubin ◽  
Christine Zardecki ◽  
Elliott M. Dolan ◽  
Changpeng Lu ◽  
Zhuofan Shen ◽  
...  
Keyword(s):  
Amino Acid ◽  
Drug Discovery ◽  
Boundary Layers ◽  
Protein Function ◽  
Active Sites ◽  
Chemical Properties ◽  
Data Bank ◽  
Three Dimensions ◽  
Sequence Variant ◽  
The Impact

AbstractThree-dimensional structures of SARS-CoV-2 and other coronaviral proteins archived in the Protein Data Bank were used to analyze viral proteome evolution during the first six months of the COVID-19 pandemic. Analyses of spatial locations, chemical properties, and structural and energetic impacts of the observed amino acid changes in >48,000 viral proteome sequences showed how each one of the 29 viral study proteins have undergone amino acid changes. Structural models computed for every unique sequence variant revealed that most substitutions map to protein surfaces and boundary layers with a minority affecting hydrophobic cores. Conservative changes were observed more frequently in cores versus boundary layers/surfaces. Active sites and protein-protein interfaces showed modest numbers of substitutions. Energetics calculations showed that the impact of substitutions on the thermodynamic stability of the proteome follows a universal bi-Gaussian distribution. Detailed results are presented for six drug discovery targets and four structural proteins comprising the virion, highlighting substitutions with the potential to impact protein structure, enzyme activity, and functional interfaces. Characterizing the evolution of the virus in three dimensions provides testable insights into viral protein function and should aid in structure-based drug discovery efforts as well as the prospective identification of amino acid substitutions with potential for drug resistance.

scholarly journals High-Throughput Screening in Academia: The Harvard Experience

2003 ◽  
Vol 8 (6) ◽  
pp. 615-619 ◽  
Author(s):  
Ross L. Stein
Keyword(s):  
Drug Discovery ◽  
High Throughput ◽  
High Throughput Screening ◽  
Harvard Medical School ◽  
Chemical Genetics ◽  
Academic Community ◽  
Successful Establishment ◽  
Day To Day Operations ◽  
Small Molecule Modulators ◽  
The Impact

To identify small-molecule modulators of biologic systems, academic scientists are beginning to use high-throughput screening (HTS) approaches that have traditionally been used only in industry. The HTS laboratories that are being established in universities, while differing in details of staffing, equipment, and size, have all been created to attain 1 or more of 3 principal goals: drug discovery, chemical genetics, or training. This article will examine the role that these activities play in 4 HTS laboratories that have been created within the academic community of Harvard Medical School and its affiliated institutions. First, the 3 activities will be defined with special attention paid to describing the impact they are having on how academic biologic science is conducted today. Next, the histories and operations of the 4 Harvard laboratories are reviewed. In the course of these summaries, emphasis is placed on understanding the motivational role that the 3 activities initially played in the creation of the 4 Harvard facilities and the roles that the activities continue to play in their day-to-day operations. Finally, several concerns are identified that must be attended to for the successful establishment and operation of an academic biologic science that has yet to be fully determined. HTS has the ability to provide the tools to test previously untestable hypotheses and can thereby allow the discovery of the unanticipated and the truly novel.

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