Blocking Play: Stopping an Allergic Response at the Molecular Level

Inappropriate response of the immune system to various antigens leads to diseases ranging from rheumatoid arthritis, multiple sclerosis and lupus, to atopic allergies such as hay fever, asthma, atopic dermatitis and food allergies. The goal of immunotherapy is to minimize allergen activation of the immune system or to disrupt the allergic response.

At the center of this image is a non-covalent inhibitor (blue molecule) in a binding pocket of a cysteine protease that modulates antigen presentation to T-cells. Drugs that inhibit proteolytic activity in this manner might curb the allergic response. X-ray crystallography, molecular modeling, NMR spectroscopy and gel electrophoresis are enabling technologies used to probe this enzyme-inhibitor complex.

Blocking Play: Stopping an Allergic Response at the Molecular Level, 2005

Ellen Sandor & (art)n: Nick Gaul and Janine Fron

Frank Axe and Hui Cai, J&JPRD, Mike Randal, Sunesis Pharmaceuticals

Virtual Photograph/PHSCologram: Duratrans, Kodalth, Plexiglas

30 x 30 inches

AZT (azido-thymidine) is a drug that is used to treat persons with AIDS. Its structure is closely related to thymidine, which is present in your DNA and in the DNA of every organism on Earth, including the HIV virus which causes AIDS. This image shows the total electron density of the molecule AZT

 

DMO

 

DMO, 2008

Ellen Sandor & (art)n:  Chris Kemp

Eric Sturman, Timothy Rydel, and William Kosinski, Monsanto Company

Virtual Photograph/PHSCologram: Duratan, Kodalith, Plexiglas

30 x 40 inches

cry-3

 

Cry-3, 2008

Ellen Sandor & (art)n: Chris Kemp

Eric Sturman, Timothy Rydel, and William Kosinski, Monsanto Company

Virtual Photograph/PHSCologram: Duratrans, Kodalth, Plexiglas

30 x 40 inches

omnitarg

Omnitarg, 2003

Ellen Sandor & (art)n: Keith Miller

Matthew Franklin, Department of Protein Engineering, Genentech

Virtual Photograph/PHSCologram: Duratrans, Kodalth, Plexiglas

40 x 30 inches

 

Open and Closed Forms of EPSP Synthase

 

Open and Closed Forms of EPSP Synthase, 2002

Ellen Sandor & (art)n: Pete Latrofa and Keith Miller

Dr. Murtaza F. Alibhai, Dr. William G. Kosinski, Dr. Douglas R. Sammas & Dr. Claire CaJacob, Monsanto Company, Dr. William C. Stallings & Dr. James R. Kiefer, Pharmacia Corporation

Stallings, W. C., Meguid-Abdel, S. S., Lim, L. W., Shieh, H.-S., Dayringer, H. E., Leimgruber, N. K., Stegeman, R. A., Anderson, K. S., Sikorski, J. A., Padgette, S. R. & Kishore, G. M. (1991) Proc. Natl. Acad. Sci. USA 88, 5046–5050, Schönbrunn, E., Eschenburg, S., Shuttleworth, W. A., Schloss, J. V., Amrhein, N., Evans, J. N. S. & Kabsch, W. (2001) Proc. Natl. Acad. Sci. U.S.A 98, 1376–1380.

Virtual Photograph/PHSCologram: Duratrans, Kodalth, Plexiglas

30 x 40 inches

cox-2

 

Shown here is the crystal structure of Celecoxib bound to cyclooxygenase-2 (COX-2). Celecoxib is a selective inhibitor of COX-2 from Searle/Monsanto that is undergoing late stage clinical trials for osteo-arthritis and rheumatoid arthritis. Pre-clinical and early clinical studies have demonstrated that celecoxib is efficacious in reducing inflammation without the typical side effects characteristic of existing nonsteroidal anti-inflammatory drugs. It is bound in the cyclooxygenase active site of COX-prostaglandins perpetuate the inflammatory response. NSAIDs also affect other inflammatory processes.

Cox-2, 1997

Ellen Sandor & (art)n: Stephan Meyers and Janine Fron

Dr. TJ O'Donnell, Ravi Kurumbail, Jennifer Pawlitz, Anna Stevens, Roderick Stegeman, James Gierse and William Stallings, Monsanto Company
Special thanks to Howard Stein, Hank Whittemore and Karen Sinsheime

Virtual Photograph/PHSCologram: Duratrans, Kodalth, Plexiglas

30 x 40 inches, and 8 x 10 inches

The COX2 protein structure using cylinders to represent the alpha-helices which are connected by loops having less regular structure. The protein has three major domains, here colored green (the egf or epidermal growth factor domain), orange (the membrane domain) and red (the catalytic domain). Embedded in the catalytic domain are a heme molecule (grey spheres) and a drug molecule acting to inhibit this enzyme. The drug is colored purple, with several atoms colored red (oxygen), blue (nitrogen) and yellow (sulphur). The drug is surrounded by a dot surface indicating how it might enter into the enzyme through the membrane domain of the protein. Finally, one of the tyrosine amino acids in the catalytic domain is shown between the heme and the inhibitor. This tyrosine is crucial to the catalytic enzymatic activity of this protein. The protein is known as COX2 or cyclo-oxygenase 2. Monsanto is developing drugs which inhbit this enzyme. These drugs act as anti-inflammatory drugs, like aspirin but without the gastro-intenstinal side-effects. Some steroids, such as cortisone have been used as anti-inflammatory drugs, but have undesirable side effects. But new, selective COX2 inhibitors are not steroids and they do not have the gastro-intenstinal side-effects of older drugs such as aspirin, ibuprofen or naproxen. These drugs are new members of an important class of drugs called non-steroidal anti-inflammatory drugs, or NSAIDs. All NSAIDs have analgesic, anti-inflammatory and antipyretic activity. They share a joint mechanism of action–blockage of the enzyme cyclo-oxygenase which is involved in the metabolism of arachidonic acid to prostaglandins. Arachidonic acid is released from membrane phospholipids in response to inflammatory stimuli. 

Human Insulin MONOMER

 

Human Insulin Monomer, 1994

Ellen Sandor & (art)n:  Stephan Meyers, Janine Fron and Craig Ahmer

Dr. James Shields and Michael Heathman, Eli LillyMolecular Modeling: Dr. James Shields, Lilly Research Laboratories, Indianapolis, IN. Structure based on X-Ray Crystallography by Professor Guy Dodson and colleagues, University of York, UKVisualization by Michael Heathman, Lilly Research Laboratories

Virtual Photograph/PHSCologram: Cibachrome, Kodalith, Plexiglas

24 x 20 inches

Human Insulin Hexamer

Human Insulin Hexamer, 1994

Ellen Sandor & (art)n:  Stephan Meyers, Janine Fron and Craig Ahmer

Dr. James Shields and Michael Heathman, Eli LillyMolecular Modeling: Dr. James Shields, Lilly Research Laboratories, Indianapolis, IN. Structure based on X-Ray Crystallography by Professor Guy Dodson and colleagues, University of York, UKVisualization by Michael Heathman, Lilly Research Laboratories

Virtual Photograph/PHSCologram: Cibachrome, Kodalth, Plexiglas

24 x 20 inches

 

Human Renin with Inhibitor

Human Renin with Inhibitor, 1991

Ellen Sandor & (art)n: Stephan Meyers, Janine Fron and Craig Ahmer

Dr. Henry Dayringer, Dr. Louis Lim and Dr. Neena Summers, Monsanto Company

Virtual Photograph/PHSCologram: Cibachrome, Kodalth, Plexiglas

24 x 20 inches

 

Manganese Superoxide Dismutase

 

Manganese Superoxide Dismutase, 1991

Ellen Sandor & (art)n: Stephan Meyers Janine From, and Craig Ahmer

William Stallings, Dr. Henry Dayringer, Katherine Pattridge, James Fee and Martha Ludwig, Monsanto Company

Virtual Photograph/PHSCologram: Cibachrome, Kodalth, Plexiglas

24 x 20 inches

contact features new work AZT-Total Electron Density

 

Contact features new work AZT-Total Electron Density, 1991

Ellen Sandor & (art)n: Stephan Meyers, Janine Fron and Craig Ahmer

Dr. TJ O'Donnell

Virtual Photograph/PHSCologram: Cibachrome, Kodalth, Plexiglas

24 x 20 inches

ddI-HOMO

 

ddI (di-deoxy-inosine) is another drug that is used to treat persons with AIDS. Its structure is similar to adenine and guanine, which are present in human DNA and in the DNA of ever other living organism on our earth, including the HIV virus, which causes AIDS. The similarity causes the virus to accept ddI, which it cannot use, instead of the adenine and guanine it needs.  This image shows the distribution of electrons in the Highest Occupied Molecular Orbital (HOMO) of ddI.

ddI-HOMO, 1991

Ellen Sandor & (art)n: Stephan Meyers, Janine Fron and Craig Ahmer

Dr. TJ O'Donnell

Virtual Photograph/PHSCologram: Cibachrome, Kodalth, Plexiglas

24 x 20 inches

Glyphosate with Water Surfaces

Glyphosate is used by farmers to kill weeds. The inner balls represent the atoms of the glyphosate molecule. The transparent blue surface is where water can touch the molecule. The gold colored surface is where water can attach to the molecule.

Glyphosate with Water Surfaces, 1991 

Ellen Sandor & (art)n: Stephan Meyers

TJ O'Donnell

 

Vintage PHSCologram: computer interleaved Crosfield Cibachrome and Kodalith films mounted on plexiglas

24 x 20 inches

 

Glycogen Phosporylase

A visualization of a molecular found in the human liver, involved in the breakdown of starches, such as those found in bread.

Glycogen Phosporylase, 1990

Ellen Sandor & (art)n: Stephan Meyers

Dr. Bob Otto, Monsanto Company

 

Vintage PHSCologram: computer interleaved Crosfield Cibachrome and Kodalith films mounted on plexiglas

24 x 20 inches

 

Round-Up Herbicide

A visualization of EPSP synthase, a molecule involved in synthetic plant growth, being blocked by glyphosate, the active component of the chemical Roundup herbicide.  
©1990 Monsanto Corporation.

Round-Up Herbicide, 1990

Ellen Sandor & (art)n:  Stephan Meyers

Dr. Bob Otto, Monsanto Company

vintage PHSCologram: computer interleaved Crosfield Cibachrome and Kodalith films mounted on plexiglas

24 x 20 inches

 

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