
Scripps Research Institute Chemists Invent Powerful Toolkit, Accelerating Creation of Potential New Drugs Method provides reactions so robust they can work in a paper cup containing Oolong tea
LA JOLLA, CA November 28, 2012 Scientists at The Scripps Research Institute (TSRI) have invented a set of chemical tools that is radically simplifying the creation of potential new drug compounds.
Pharmaceutical chemists frequently seek to generate dozens or even hundreds of variations of a given compound to see which works best. The new toolkit described in the November 28, 2012 issue of the journal Nature makes this process easier and cheaper, enabling previously time- and cost-prohibitive chemical modifications. This fundamental innovation is already being adopted by drug companies and is expected to speed the development of new compounds in other industries as well.
Feedback from companies that have started to use this toolkit indicates that it solves a real problem for them by boosting their chemists' productivity and by expanding the realm of compounds that they can feasibly generate, said Phil S. Baran, PhD, a professor in the Department of Chemistry and a member of the Skaggs Institute for Chemical Biology at TSRI who led the work.
Robert Lees, PhD, of the National Institutes of Health's National Institute of General Medical Sciences, which partially funded the work, added, Methods to predictably, selectively and efficiently functionalize a given C-H site are difficult to invent but highly significant for developing new therapeutic and diagnostic agents, and studying biomolecules. Practical chemistry for introducing fluorine atoms into organic compounds is also an important current need in medicinal chemistry. The new reagents developed by Professor Baran address both goals, and they will likely be widely utilized in both academic and industrial laboratories.
A Common and Useful Structure
The toolkit is a set of newly invented chemicals and methods for attaching functional groups of molecules to a series of common chemical structures known as nitrogen-containing heterocycles flat molecules with rings made of carbon atoms and at least one nitrogen atom. Though their name might seem esoteric, these structures are common in both natural and synthetic chemicals, and they are found in most drugs that are taken in pill form.
Ironically, the properties that make nitrogen-containing structures so useful in medicines are what also make them so hard to modify, said Baran. The resistance of nitrogen heterocycles to modification by traditional techniques has slowed drug discovery and has put many potential modifications out of reach.
But Baran envisioned a different scenario. The ideal for discovery chemists would be a method that works in water, in an open flask, with procedures that are simple enough to be automated, he said.
A few years ago Baran began to glimpse the possibility of achieving such a method. His lab had just succeeded in synthesizing a complex natural nitrogen heterocycle, palau'amine, a toxin made by sea sponges in the Western Pacific that has shown anticancer, antibacterial and antifungal pharmaceutical promise. As we developed an understanding of how that compound reacts, we recognized that it might help us solve this larger problem that discovery chemists face, he said.
The nitrogen atoms in heterocycles are what make them so tricky to handle. Traditional methods of modification typically aim to block their influence before the addition of any modifying molecules, but this approach can be cumbersome and expensive. The experience with palau'amine, which features an extremely challenging nine nitrogen atoms per molecule, led Baran and his team to try to find chemical reagents tools, in effect that would modify heterocycles directly.
A More Direct Route
Direct methods already had existed, but they often require extreme temperatures as well as expensive and hazardous reagents. During 2010 and 2011, Baran's lab experimented with several comparatively safe chemical reagents that can work in mild conditions to make commonly desired heterocycle modifications, such as the addition of a difluoromethyl group. One of these new reagents, a zinc dialkylsulfinate salt (DFMS) designed to transfer the difluoromethyl group, turned out to work particularly well. We quickly realized that we might be able to make related zinc sulfinate salts that would attach other functional groups to heterocycles, Baran said.
In the new report in Nature, Baran and his colleagues describe an initial toolkit consisting of ten of these zinc-based salts, each of which attaches a different functional group to a heterocycle framework. We selected these groups because they are commonly used by medicinal chemists, said Fionn O'Hara, PhD, a postdoctoral researcher in the Baran laboratory who was a first author of the new report with postdoctoral researcher Yuta Fujiwara, PhD, and technician Janice A. Dixon.
In many cases, chemists will be able to use these reagents sequentially to make more than one modification to a starting compound, noted Fujiwara. The groups that can be attached with the new reagents include trifluoromethyl, difluoromethyl, trifluoroethyl, monofluoromethyl, isopropyl and triethylene glycol monomethyl ether.
To demonstrate the ability of the reagents to work in biological media, Baran's team used them to difluoromethylate or trifluoromethylate heterocycles in a solution of cell lysate the contents of cells as well as to serve as a buffer medium, Tris, commonly used in lab-dish tests. To underscore the general robustness of the reagents, the team even carried out such modifications in a paper cup containing Oolong tea.
Baran's laboratory collaborated in the research with scientists from the pharmaceutical company Pfizer Inc. They provided
Most recent headlines
13/03/2025
(L-R) Stephanie Suganami, Tatanka Means, John Malkovich, Ayo Edebiri, and Juliette Lewis attend the premiere of Opus at Eccles Theatre in Park City. (Photo by...
13/03/2025
Spotify took center stage at the London Book Fair this week, reaffirming our commitment to the audiobook market and showcasing our impact on the publishing indu...
13/03/2025
At Spotify, we work every day to lift up new voices, giving creators the opportunity to live off their art. Through Spotify Audiobooks, our in-house publishing ...
13/03/2025
Every time airborne law enforcement (ALE) teams fly, they expect their equipment to perform. Whether airborne units are conducting support for ground teams, bor...
13/03/2025
Sunday February 9 saw the annual return of the US' biggest television event, the Super Bowl LIX. Jamie McCombs, Fox Sports Audio Consultant / Sr. Audio capt...
13/03/2025
On Sunday March 2, stars across the film industry gathered at the Dolby Theatre in Los Angeles for the 97th Academy Awards. Production Sound Mixer Paul Sandweis...
13/03/2025
WUPPERTAL, Germany Riedel Communications will feature its new StageLink family of smart edge devices, Smart Audio and Mixing Engine (SAME) and Virtual Smart Pan...
13/03/2025
TAG Video Systems and Harmonic Partner to Deliver Enhanced Real-Time Monitoring ...
13/03/2025
DigitalGlue Invites NAB Visitors to Experience New Features in Managed Storage P...
13/03/2025
FOR-A America Theme - Connecting the Present, Building the Future - Comes to Lif...
13/03/2025
CTIA, the wireless industry association, has named former FCC Chairman Aji Pai as its President and Chief Executive Officer, effective April 1. He replaces Mere...
13/03/2025
he National Association of Broadcasters is urging the FCC to end its investigation of that controversial CBS interview with Kamala Harris stating there is no ...
13/03/2025
MIAMI CBS News & Stations continues to expand its use of augmented and virtual reality technologies with the planned launch of an augmented reality/virtual real...
13/03/2025
Srividhya Srinivasan, co-founder and chief customer success & innovation Officer at Amagi, tells TVBEurope how staying ahead of the latest trends is essential f...
13/03/2025
WASHINGTON FCC Chairman Brendan Carr announced that the agency has launched a massive, new deregulatory initiative that could potentially subject virtually all ...
13/03/2025
SUNNYVALE, Calif. SDVI has announced that it has integrated its Rally media supply chain management platform with the Spectra Vail multi-cloud data management s...
13/03/2025
ATLANTA Gray Media has announced that the Federal Communications Commission (FCC) has granted a waiver of its local ownership rules to permit Gray Media to acqu...
13/03/2025
TV Tech: What do you anticipate will be the most significant technology trends at the 2025 NAB Show?...
13/03/2025
Watch Student Naomi Soleils Folk Pop Performance on The Voice The songwriting major sang Stars by Grace Potter and the Nocturnals during the blind auditions.
...
13/03/2025
Roku Debuts NWSL Zone' Within Roku Sports to Spotlight Live Games, Content Feature marks Rokus first women's league-branded zone within service By Bra...
13/03/2025
Pixels, Images, Video, AI - and Us: A Perspective on AI from NDI Inventor Andrew...
13/03/2025
SVG New Sponsor Spotlight: Lighting Design Group's Steve Brill, Dennis Size ...
13/03/2025
IOC, Comcast NBCU Ink $3B Media-Rights Extension for Olympic Games Through 2036;...
13/03/2025
NCAA March Madness Live Returns with Expanded Availability of MultiView Vertical...
13/03/2025
SVG Sit-Down: Cosm's Devin Poolman on What It Takes To Deliver the Immersive...
13/03/2025
Sky Business, Sky's B2B division, providing connectivity and content to busi...
13/03/2025
Rohde & Schwarz launches R&S NRP140TWG(N) thermal power sensor: A new benchmark ...
13/03/2025
We asked the questions, analysed the answers and now we're excited to share the results of the fifth edition of the ICG Marketing Survey.
Our 2025 survey p...
13/03/2025
SAN JOSE, Calif. - March 13, 2025 Harmonic (NASDAQ: HLIT) today announced a breakthrough in video streaming innovation with the launch of new origin capabilitie...
13/03/2025
Haivision Showcases Mission-Critical Video Solutions at SOF Week 2025
Haivision's video wall systems, ISR technology, and DoDIN APL-certified video distri...
13/03/2025
Company Leads the Way with New Software-Based Production Platform, 12G Switcher,...
13/03/2025
A new Apple Immersive concert experience, Metallica, is coming to Apple Vision Pro this Friday, March 14. Filmed in Mexico City during the sold-out second-year ...
13/03/2025
Here is your host, Patrick Kielty!
Shake your Shamrocks, Patrick Kielty will be...
13/03/2025
This St. Patrick's weekend, RT invites you to celebrate all things Irish, showcasing the very best of Irish sport, entertainment and live coverage from the...
13/03/2025
What's next in AI is at GTC 2025. Not only the technology, but the people and ideas that are pushing AI forward - creating new opportunities, novel solution...
13/03/2025
Facebook
Twitter
LinkedIn
By combining T-Mobile's robust network, Thal...
13/03/2025
Bundle up - GeForce NOW is bringing a flurry of Blizzard titles to its ever-expanding library.
Prepare to weather epic gameplay in the cloud, tackling the genr...
13/03/2025
AI is leveling up the world's most beloved games, as the latest advancements...
13/03/2025
PC game modding is massive, with over 5 billion mods downloaded annually. Mods p...
12/03/2025
O Spotify acaba de lan ar o relat rio Loud & Clear deste ano, uma vis o transpar...
12/03/2025
Spotify acaba de presentar el informe Loud & Clear de este a o, una mirada trans...
12/03/2025
Ramadan, a period of profound spiritual significance for Muslims worldwide, is a time for fasting, prayer, reflection, and community. Enrich your experience thi...
12/03/2025
Spotify has just unveiled this year's Loud & Clear report, a transparent loo...
12/03/2025
More than 70% of FAST programming has been produced since 2010, according to new Gracenote report
NEW YORK March 12, 2025 Gracenote, the content data busin...
12/03/2025
GEONA, Nev. Independent digital and linear advertising rep firm Viamedia will adopt cloud-based ShowSeeker Pilot as its primary ad campaign and order management...
12/03/2025
BRUSSELS Mediagenix has announced that Wael Yasin has joined the company as sales director Central Europe....
12/03/2025
LONDON A new study highlights opportunities for shoppable TV and the massive impact online consumer spending is having on the economy, with Omdia predicting tha...
12/03/2025
CUPERTINO, Calif. Interra Systems has announced that Comcast Technology Solutions has integrated recent updates to BATON Version 9 into its operations....
12/03/2025
Nevion announces new 400G addition to its eMerge SDN media fabric offering
Brie Clayton March 12, 2025
0 Comments
High-capacity switch enhances existi...
12/03/2025
DaVinci Resolve Studio Delivers Cinematic Sound for Adam Bol
Brie Clayton March 12, 2025
0 Comments
Feature film relies on DaVinci Resolve Studio for ...