Beyond the Molecular Frontier Challenges for Chemistry and Chemical Engineering (2003) / Chapter Skim
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7 The Interface with Biology and Medicine
7 The Interface with Biology and Medicine
Pages 95-122
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From page 95... ...
7 The Interface with Biology and Medicine1 1As part of the overall project on Challenges for the Chemical Sciences in the 21st Century, a workshop on Health and Medicine will lead to a separate report. The reader is urged to consult that report for further information.
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From page 96... ...
Nowhere has the role of chemical sciences been better illustrated than in the discovery, development, and production of new medicines and ways in which we can more selectively deliver these medicines to the organ or tissue where they are needed. This fundamental understanding of what chemical transformations occur in living creatures, how these chemical transformations are regulated, and how they respond to extracellular stimuli is also critical to developing semisynthetic tissues and organs as replacements for damaged organs, to gene therapy, and to solving a host of clinical problems.
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From page 97... ...
Molecular analysis of living cells has led to a flow plan of information in molecular biology, known as the Central Dogma: The information necessary for a cell is encoded in the double helix of DNA. DNA acts as a template for its own replication, and segments of DNA that encode information for the primary structure (i.e., amino acid sequence)
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From page 98... ...
This proteolysis occurs at the very end of the HIV replication cycle (Figure 7-1~. The three-dimensional structural information derived from the x-ray crystal structure, combined with computer modeling techniques, allowed chemists to design potent, selective inhibitors of the protease enzyme (Figure
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From page 99... ...
to block incorporation of the viral genome into the host cell, and (b) HIV protease inhibitors (enlargement, lower right)
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From page 100... ...
Thus a single protein, derived from a single gene, can be transformed into numerous distinct molecular species and thereby amplify the information content of a very concise genome. Comparisons have shown that post-translational modifications are more extensive in higher organisms.
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From page 101... ...
Much of biochemical engineering activity is directed toward human health and forms an important branch of biomedical engineering, particularly in activities such as drug delivery devices, artificial organs, and tissue engineering (e.g., artificial skin for burn victims)
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From page 102... ...
Examples of some of these products are tissue plasminogen activator used to treat stroke and heart attack patients, erythropoietin to treat anemia resulting from kidney damage or chemotherapy, and granulocyte colony stimulating factor as an adjuvant to chemotherapy and cancer treatment. Another accomplishment has been the development of effective devices for the controlled release of pharmaceuticals and therapeutic proteins.
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From page 103... ...
. In addition, chemists have developed a better understanding of the modular cellular machinery used to synthesize natural products and have used the techniques of metabolic engineering to harness these modular processes to create novel molecules.
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From page 105... ...
Decoding these mysteries and producing a detailed molecular picture of how things work is a critical step. However, nowhere has the role of chemistry been better illustrated than in the creation and development of new medicines and therapies.
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From page 107... ...
THE INTERFACE WITH BIOLOGY AND MEDICINE 107 Underlying the discovery of a selective asthma therapy are numerous advances in analytical and instrumental techniques as well as synthetic methods that allow the construction of complex molecules. Practical catalytic, stereospecific, and organometallic methods that permit a high level of stereochemical control have enabled production at the multiton level of molecules previously inaccessible even at the gram scale.
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110 BEYOND THE MOLECULAR FRONTIER Cohen roxen spirin haciin ibup nap indometi kett rofecc melon celec~ nimes diclof. plroxl' at.
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From page 111... ...
THE INTERFACE WITH BIOLOGY AND MEDICINE 111 CHALLENGES AND OPPORTUNITIES FOR THE FUTURE The opportunities for discovery and invention at the interface of chemistry, engineering, and biology are enormous, and many examples have been described in the preceding sections. This interface represents a true research frontier one that is critical to our ability to develop new chemistry for the prevention, diagnosis, and treatment of human disease.
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From page 113... ...
We will need to isolate the proteins that are the gene products,
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From page 114... ...
Indeed, a major intellectual challenge to the chemical sciences is developing a systematic framework and computational tools to relate microarray data, as well as data on protein levels, to a description of the dynamic regulatory networks controlling cellular functions. Proteomics is a combination of experimental and analytical tools to determine the total protein content of a cell or tissue.
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From page 115... ...
Insights from genetics may help guide us toward elegant and rational cures, but we will also make use of screens to identify natural products and libraries of randomly generated synthetic compounds (combinatorial chemistry)
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From page 116... ...
Because cells and the body respond not only to genetic information but also to environmental cues, any analysis must take into account the time and environment-dependent nature of the biological system. Because of their training in analysis of integrated systems, biochemical engineers should be able to contribute integrated, quantitative models of these biological systems to guide the selection of targets for intervention and the synthesis of a precise delivery system.
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From page 117... ...
This device would effectively mimic the responses of the natural pancreas. Other delivery systems may mimic viruses for DNA delivery to specific target cells as a more controllable method for gene therapy.
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From page 118... ...
Replication, transcription, and translation, as well as other critical cellular functions, appear to be carried out through the function of multiprotein/nucleic acid particles. Advances in x-ray crystallography coupled with other imaging methods such as NMR and electron microscopy are now providing our first snapshots of these macromolecular machines, such as the ribosome in which proteins are synthesized in the cell.
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From page 119... ...
Are macromolecular assemblies of such complexity required to carry out these functions? Indeed, can we next begin to design novel macromolecular machines to carry out new, still more complex functions?
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From page 121... ...
While the engineering of tissue constructs has had commercial success, highly perfused or vascularized tissue remains problematic. Artificial organs, such as an artificial liver, remain objects of intense research.
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From page 122... ...
In addition, ways are needed to integrate better genomic, proteomic, and advanced computational methods with metabolic engineering to inexpensively produce large amounts of nonprotein products. This listing of challenges for the future is not exhaustive, but it should provide the reader with a sense of vast possibilities for the interface of the chemical sciences and engineering with biology.
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