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Distributed Drug Discovery, Part 1: linking academia and combinatorial chemistry to find drug leads for developing world diseases.

Scott WL, O'Donnell MJ - J Comb Chem (2009 Jan-Feb)

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and Chemical Biology, Indiana University-Purdue University Indianapolis, Indianapolis, Indiana 46202-3274, USA. wscott@iupui.edu

ABSTRACT

This Perspective describes, both conceptually and in practical embodiment, a project developed at IUPUI that we call Distributed Drug Discovery (D3). This cross-disciplinary program is grounded in the conviction that the major challenge of developing drug leads for neglected diseases can be addressed, at low cost and significant educational benefit, through a distributed combinatorial discovery process. This will be accomplished by dividing the computational, synthesis, and screening stages of drug discovery into smaller units and developing simple procedures and inexpensive equipment to permit students, worldwide, to be the problem solvers during their normal educational studies. This connects them, in their training, to an ultimate application of the skills and expertise they are learning. At the same time it enables the problem of drug-lead discovery to be economically addressed. Once drug leads are identified, other nonprofit initiatives can shepherd them through the numerous steps remaining to convert these leads into approved drugs, and make them available, at low cost, to those in need.

Distributed computation is now well documented in drug discovery. This Perspective focused on how combinatorial chemistry can be utilized to enable the virtual catalog and synthesis components of D3. When distributed screening methodologies are developed, the overall integrated process will be in place. The chemistry component of D3 envisions two students (perhaps one in an undergraduate organic laboratory in a developing world country and the other in a laboratory in the developed world) synthesizing, in duplicate, the lead molecule that is subsequently turned into a drug to treat malaria, AIDS, tuberculosis, leischmaniasis, trypanosomiasis, or some other disease widely affecting the developing world. It is our hope that D3 will be a unifying concept encouraging our colleagues throughout the world to join us in developing and harnessing distributed global resources for education, human development, and the discovery of drug leads for developing world and other neglected diseases.

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Bill-Board equipment for Distributed Drug Discovery.
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fig4: Bill-Board equipment for Distributed Drug Discovery.

Mentions: Carrying out D3 chemistry requires simple and low-cost equipment. While there are numerous devices for conducting solid-phase reactions, most do not meet the D3 constraint of simplicity, low cost, reusability, and especially, appropriate student scale. We initially explored, at the Miami University NSF Workshop, the use of equipment capable of conducting 24 combinatorial reactions at a time. However, it was clear that it would be an overwhelming challenge to use in most undergraduate laboratories. To proceed further, the equipment, which was originally developed in industry,(41) was redesigned to carry out six solid-phase reactions at a time, on a 25 to 200 μmol scale, in a 2 × 3 combinatorial grid. The 3.5 mL reaction vessels, with screw caps on both ends and a fused frit at one end, are made out of glass. This provides inertness, durability, and long-term vessel reusability, making these reaction vessels cost competitive with disposable plastic cartridges. A picture of the kit, known as a “Bill-Board 6-pack”, is shown in Figure 4. The Bill-Board 6-pack kit is manufactured locally at modest cost.(42)


Distributed Drug Discovery, Part 1: linking academia and combinatorial chemistry to find drug leads for developing world diseases.

Scott WL, O'Donnell MJ - J Comb Chem (2009 Jan-Feb)

Bill-Board equipment for Distributed Drug Discovery.
© Copyright Policy - open-access - ccc-price
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2651689&req=5

fig4: Bill-Board equipment for Distributed Drug Discovery.
Mentions: Carrying out D3 chemistry requires simple and low-cost equipment. While there are numerous devices for conducting solid-phase reactions, most do not meet the D3 constraint of simplicity, low cost, reusability, and especially, appropriate student scale. We initially explored, at the Miami University NSF Workshop, the use of equipment capable of conducting 24 combinatorial reactions at a time. However, it was clear that it would be an overwhelming challenge to use in most undergraduate laboratories. To proceed further, the equipment, which was originally developed in industry,(41) was redesigned to carry out six solid-phase reactions at a time, on a 25 to 200 μmol scale, in a 2 × 3 combinatorial grid. The 3.5 mL reaction vessels, with screw caps on both ends and a fused frit at one end, are made out of glass. This provides inertness, durability, and long-term vessel reusability, making these reaction vessels cost competitive with disposable plastic cartridges. A picture of the kit, known as a “Bill-Board 6-pack”, is shown in Figure 4. The Bill-Board 6-pack kit is manufactured locally at modest cost.(42)

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and Chemical Biology, Indiana University-Purdue University Indianapolis, Indianapolis, Indiana 46202-3274, USA. wscott@iupui.edu

ABSTRACT

This Perspective describes, both conceptually and in practical embodiment, a project developed at IUPUI that we call Distributed Drug Discovery (D3). This cross-disciplinary program is grounded in the conviction that the major challenge of developing drug leads for neglected diseases can be addressed, at low cost and significant educational benefit, through a distributed combinatorial discovery process. This will be accomplished by dividing the computational, synthesis, and screening stages of drug discovery into smaller units and developing simple procedures and inexpensive equipment to permit students, worldwide, to be the problem solvers during their normal educational studies. This connects them, in their training, to an ultimate application of the skills and expertise they are learning. At the same time it enables the problem of drug-lead discovery to be economically addressed. Once drug leads are identified, other nonprofit initiatives can shepherd them through the numerous steps remaining to convert these leads into approved drugs, and make them available, at low cost, to those in need.

Distributed computation is now well documented in drug discovery. This Perspective focused on how combinatorial chemistry can be utilized to enable the virtual catalog and synthesis components of D3. When distributed screening methodologies are developed, the overall integrated process will be in place. The chemistry component of D3 envisions two students (perhaps one in an undergraduate organic laboratory in a developing world country and the other in a laboratory in the developed world) synthesizing, in duplicate, the lead molecule that is subsequently turned into a drug to treat malaria, AIDS, tuberculosis, leischmaniasis, trypanosomiasis, or some other disease widely affecting the developing world. It is our hope that D3 will be a unifying concept encouraging our colleagues throughout the world to join us in developing and harnessing distributed global resources for education, human development, and the discovery of drug leads for developing world and other neglected diseases.

Show MeSH