Nanotechnology Now

Our NanoNews Digest Sponsors

Heifer International

Wikipedia Affiliate Button

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

Biosensors: Distance makes the signal grow stronger March 1st, 2017

Smart multi-layered magnetic material acts as an electric switch: New study reveals characteristic of islands of magnetic metals between vacuum gaps, displaying tunnelling electric current March 1st, 2017

Bioinspired process makes materials light, robust, programmable at nano- to macro-scale: Ultralight web of silk nano fibers withstands load 4,000 times its weight February 28th, 2017

NovAliX Turns to High-Resolution Cryo-Transmission Electron Microscopy for Pre-Clinical Drug Discovery Research: Thermo Fisher Scientificís Cryo-TEM provides critical information for small molecule and biologic drug discovery February 28th, 2017

Chemistry

Molecular phenomenon discovered by advanced NMR facility: Cutting edge technology has shown a molecule self-assembling into different forms when passing between solution state to solid state, and back again - a curious phenomenon in science - says research by the University of Wa February 22nd, 2017

In-cell molecular sieve from protein crystal February 14th, 2017

Nano-level lubricant tuning improves material for electronic devices and surface coatings February 11th, 2017

Scientists determine precise 3-D location, identity of all 23,000 atoms in a nanoparticle: Berkeley Lab researchers help to map iron-platinum particle in unprecedented detail February 6th, 2017

Govt.-Legislation/Regulation/Funding/Policy

Bioinspired process makes materials light, robust, programmable at nano- to macro-scale: Ultralight web of silk nano fibers withstands load 4,000 times its weight February 28th, 2017

Nano 'sandwich' offers unique properties: Rice University researchers simulate two-dimensional hybrids for optoelectronics February 27th, 2017

Sandia use confined nanoparticles to improve hydrogen storage materials performance: Big changes from a small package for hydrogen storage February 25th, 2017

Atom-scale oxidation mechanism of nanoparticles helps develop anti-corrosion materials February 24th, 2017

Nanomedicine

Biosensors: Distance makes the signal grow stronger March 1st, 2017

NovAliX Turns to High-Resolution Cryo-Transmission Electron Microscopy for Pre-Clinical Drug Discovery Research: Thermo Fisher Scientificís Cryo-TEM provides critical information for small molecule and biologic drug discovery February 28th, 2017

New nano approach could cut dose of leading HIV treatment in half February 24th, 2017

Atomic force imaging used to study nematodes: KFU bionanotechnology lab (head - Dr. Rawil Fakhrullin) has obtained 3-D images of nematodes' cuticles February 23rd, 2017

Discoveries

Biosensors: Distance makes the signal grow stronger March 1st, 2017

Smart multi-layered magnetic material acts as an electric switch: New study reveals characteristic of islands of magnetic metals between vacuum gaps, displaying tunnelling electric current March 1st, 2017

Bioinspired process makes materials light, robust, programmable at nano- to macro-scale: Ultralight web of silk nano fibers withstands load 4,000 times its weight February 28th, 2017

NovAliX Turns to High-Resolution Cryo-Transmission Electron Microscopy for Pre-Clinical Drug Discovery Research: Thermo Fisher Scientificís Cryo-TEM provides critical information for small molecule and biologic drug discovery February 28th, 2017

Announcements

Biosensors: Distance makes the signal grow stronger March 1st, 2017

Smart multi-layered magnetic material acts as an electric switch: New study reveals characteristic of islands of magnetic metals between vacuum gaps, displaying tunnelling electric current March 1st, 2017

Bioinspired process makes materials light, robust, programmable at nano- to macro-scale: Ultralight web of silk nano fibers withstands load 4,000 times its weight February 28th, 2017

NovAliX Turns to High-Resolution Cryo-Transmission Electron Microscopy for Pre-Clinical Drug Discovery Research: Thermo Fisher Scientificís Cryo-TEM provides critical information for small molecule and biologic drug discovery February 28th, 2017

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