Nanotechnology Now





Heifer International

Wikipedia Affiliate Button


DHgate

Home > Press > Scripps research scientists develop brand new class of small molecules through innovative chemistry

This is Scripps Research Associate Professor Glenn Micalizio.

Credit: Photo Courtesy of the Scripps Research Institute
This is Scripps Research Associate Professor Glenn Micalizio.

Credit: Photo Courtesy of the Scripps Research Institute

Abstract:
Inspired by natural products, scientists on the Florida campus of the Scripps Research Institute have created a new class of small molecules with the potential to serve as a rich foundation for drug discovery.

Scripps research scientists develop brand new class of small molecules through innovative chemistry

Jupiter, FL | Posted on November 21st, 2011

Combining the power of synthetic chemistry with some advanced screening technologies, the new approach could eventually expand by millions the number of provocative synthetic compounds available to explore as potential drug candidates. This approach overcomes substantial molecular limitations associated with state-of-the-art approaches in small molecule synthesis and screening, which often serve as the foundation of current drug discovery efforts.

The study, led by Scripps Research Associate Professor Glenn Micalizio, was published Nov. 20, 2011, in an advanced online edition of the journal Nature Chemistry.

To frame the significance of this advance, Micalizio explains that high-throughput screening is an important component of modern drug discovery. In high-throughput screening, diverse collections of molecules are evaluated en masse for potential function in a biological area of interest. In this process, success is critically dependent on the composition of the molecular collections under evaluation. Modern screening centers maintain a relatively static collection of molecules, the majority of which are commercially available materials that have structures unrelated to natural products -- molecules that are appreciated as validated leads for drug development.

"This divergence in structure between natural products and commercially available synthetics lies at the heart of our inquiry," said Micalizio. "Why should we limit discovery of therapeutic leads to compound collections that are influenced by concerns relating to commercial availability and compatibility with an artificial set of constraints associated with the structure of modern screening centers?"

To expand the compounds available for investigation, the scientists embraced an approach to structural diversity that mimics nature's engine for the discovery of molecules with biological function. This process, termed "oligomerization," is a modular means of assembling structures (akin to the way that letters are used in a sequence to provide words with meaning) where a small collection of monomeric units can deliver a vast collection of oligomeric products of varying length, structure, and function (like the diversity of words presented in a dictionary).

Coupling this technique with a synthetic design aimed at generating molecules that boast molecular features inspired by the structures of bioactive natural products (specifically, polyketide-derived natural products, which include erythromycin, FK-506, and epothilone), the scientists established a new chemical platform for the discovery of potential therapeutics.

Micalizio points out: "The importance of oligomerization to drive discovery is well appreciated in chemistry and biology, yet a means to realize this process as an entry to small molecule natural product-inspired structures has remained elusive. The crux of the problem is related to challenges associated with the control of shape for each member of a complex oligomer collection -- the central molecular feature that defines biological function."

"It is the stability associated with the shape of these new compounds that lies at the heart of the practical advance," he continued. "The unique features of this science now make possible the ability to synthesize large collections of diverse natural product-inspired structures that have predictable and stable three-dimensional shapes."

Micalizio said that the science described represents a first step toward revolutionizing discovery at the interface of chemistry, biology, and medicine by embracing nature's strategy for molecular discovery. Coupling this type of advance with modern screening technology that can handle the evaluation of large compound collections at low cost (such as work by Scripps Florida Professor Thomas Kodadek, a co-author of the new study), can dramatically enhance the future of pharmaceutically relevant science.

The potential of this vision was highlighted in the new study, in which a 160,000-member compound collection was employed to discover the first non-covalent small molecule ligand to the DNA binding domain of p53 -- an important transcription factor that regulates a variety of genes involved in cell cycle control and cell death.

The first author of the study, "A Biomimetic Polyketide-Inspired Approach to Small-Molecule Ligand Discovery," is Claudio Aquino of Scripps Research. In addition to Micalizio and Kodadek, other authors include Mohosin Sarkar, Michael J. Chalmers, and Kimberly Mendes.

The study was supported by the Fidelity Biosciences Research Initiative, The State of Florida (The Florida Funding Corporation), and the National Institutes of Health.

####

About Scripps Research Institute
The Scripps Research Institute is one of the world's largest independent, non-profit biomedical research organizations. Scripps Research is internationally recognized for its discoveries in immunology, molecular and cellular biology, chemistry, neuroscience, and vaccine development, as well as for its insights into autoimmune, cardiovascular, and infectious disease. Headquartered in La Jolla, California, the institute also includes a campus in Jupiter, Florida, where scientists focus on drug discovery and technology development in addition to basic biomedical science. Scripps Research currently employs about 3,000 scientists, staff, postdoctoral fellows, and graduate students on its two campuses. The institute's graduate program, which awards Ph.D. degrees in biology and chemistry, is ranked among the top ten such programs in the nation.

For more information, please click here

Contacts:
Mika Ono

858-784-2052

Copyright © Scripps Research Institute

If you have a comment, please Contact us.

Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.

Bookmark:
Delicious Digg Newsvine Google Yahoo Reddit Magnoliacom Furl Facebook

Related News Press

News and information

Physicists solve quantum tunneling mystery: ANU media release: An international team of scientists studying ultrafast physics have solved a mystery of quantum mechanics, and found that quantum tunneling is an instantaneous process May 27th, 2015

Nanotechnology identifies brain tumor types through MRI 'virtual biopsy' in animal studies: If results are confirmed in humans, tumor cells could someday be diagnosed by MRI imaging and treated with tumor-specific IV injections; new NIH grant will fund future study May 27th, 2015

Who needs water to assemble DNA? Non-aqueous solvent supports DNA nanotechnology May 27th, 2015

Controlled Release of Anticorrosive Materials in Spot by Nanocarriers May 27th, 2015

Production of Copper Cobaltite Nanocomposites with Photocatalytic Properties in Iran May 27th, 2015

Chemistry

Production of Copper Cobaltite Nanocomposites with Photocatalytic Properties in Iran May 27th, 2015

This Slinky lookalike 'hyperlens' helps us see tiny objects: The photonics advancement could improve early cancer detection, nanoelectronics manufacturing and scientists' ability to observe single molecules May 23rd, 2015

Conversion of Greenhouse Gases to Syngas in Presence of Nanocatalysts in Iran May 22nd, 2015

Govt.-Legislation/Regulation/Funding/Policy

Nanotechnology identifies brain tumor types through MRI 'virtual biopsy' in animal studies: If results are confirmed in humans, tumor cells could someday be diagnosed by MRI imaging and treated with tumor-specific IV injections; new NIH grant will fund future study May 27th, 2015

Who needs water to assemble DNA? Non-aqueous solvent supports DNA nanotechnology May 27th, 2015

One step closer to a single-molecule device: Columbia Engineering researchers first to create a single-molecule diode -- the ultimate in miniaturization for electronic devices -- with potential for real-world applications May 25th, 2015

DNA Double Helix Does Double Duty in Assembling Arrays of Nanoparticles: Synthetic pieces of biological molecule form framework and glue for making nanoparticle clusters and arrays May 25th, 2015

Nanomedicine

Nanotechnology identifies brain tumor types through MRI 'virtual biopsy' in animal studies: If results are confirmed in humans, tumor cells could someday be diagnosed by MRI imaging and treated with tumor-specific IV injections; new NIH grant will fund future study May 27th, 2015

Who needs water to assemble DNA? Non-aqueous solvent supports DNA nanotechnology May 27th, 2015

DNA Double Helix Does Double Duty in Assembling Arrays of Nanoparticles: Synthetic pieces of biological molecule form framework and glue for making nanoparticle clusters and arrays May 25th, 2015

Nanostructures Increase Corrosion Resistance in Metallic Body Implants May 24th, 2015

Discoveries

Physicists solve quantum tunneling mystery: ANU media release: An international team of scientists studying ultrafast physics have solved a mystery of quantum mechanics, and found that quantum tunneling is an instantaneous process May 27th, 2015

Nanotechnology identifies brain tumor types through MRI 'virtual biopsy' in animal studies: If results are confirmed in humans, tumor cells could someday be diagnosed by MRI imaging and treated with tumor-specific IV injections; new NIH grant will fund future study May 27th, 2015

Who needs water to assemble DNA? Non-aqueous solvent supports DNA nanotechnology May 27th, 2015

Production of Copper Cobaltite Nanocomposites with Photocatalytic Properties in Iran May 27th, 2015

Announcements

Physicists solve quantum tunneling mystery: ANU media release: An international team of scientists studying ultrafast physics have solved a mystery of quantum mechanics, and found that quantum tunneling is an instantaneous process May 27th, 2015

Nanotechnology identifies brain tumor types through MRI 'virtual biopsy' in animal studies: If results are confirmed in humans, tumor cells could someday be diagnosed by MRI imaging and treated with tumor-specific IV injections; new NIH grant will fund future study May 27th, 2015

Who needs water to assemble DNA? Non-aqueous solvent supports DNA nanotechnology May 27th, 2015

Controlled Release of Anticorrosive Materials in Spot by Nanocarriers May 27th, 2015

NanoNews-Digest
The latest news from around the world, FREE




  Premium Products
NanoNews-Custom
Only the news you want to read!
 Learn More
NanoTech-Transfer
University Technology Transfer & Patents
 Learn More
NanoStrategies
Full-service, expert consulting
 Learn More










ASP
Nanotechnology Now Featured Books




NNN

The Hunger Project