A new kind of molecular differentness Chemists' discovery of a small bacterial molecule with natural and inside-out' versions could have implications for future drug development
January 02, 2020
LA JOLLA, CA Chemists at Scripps Research have found a new way in which small organic molecules, despite having the same chemical formula and all the same chemical bonds, can differ in shape and therefore in their biological properties.
The chemists, who report their discovery in a paper in Science, found that a mysterious molecule called tryptorubin A, which is made only by certain bacteria that live in ant colonies, can be synthesized in the natural form or in a strange-looking alternative form that is essentially inside out.
This unusual type of shape variation, called non-canonical atropisomerism, has never been observed in a small molecule before. Small molecules are of special interest for chemists because most drugs are made of them their small size allows them to survive the digestion process when in pill form.
The ways in which a small molecule can vary in shape when it is synthesized are important too because often only one shape variant, or isomer, has the desired biological activity.
The Scripps Research chemists in this case were able to devise a technique to synthesize either the natural form of tryptorubin A or the unnatural, inside-out isomer.
I think our new awareness of this complex isomerism that can occur in small molecules, and the possible necessity of driving a synthesis towards one isomer or the other, are ultimately going to be relevant to the development of new drugs, says study lead author Solomon Reisberg, a graduate student in the laboratory of Phil Baran, PhD, the Darlene Shiley Chair in Chemistry at Scripps Research.
The study was a collaboration between the Baran Laboratory and the laboratory of chemist Jon Clardy, PhD, a professor of biological chemistry and molecular pharmacology at Harvard Medical School. Clardy and his colleagues isolated tryptorubin A in 2017 in the course of studying the symbiosis among ants, the fungus they farm for food, and the bacterial species that live on the fungus. The newly discovered compound, which has an oddly globular shape despite its small size, is produced by at least one species of fungus-associated Streptomyces bacteria.
No one yet understands tryptorubin A's natural function, Reisberg says. All that's known for sure is that it is found only when all three species ants, fungus, bacteria are around, so possibly it has a signaling role.
For the Baran lab, which specializes in finding new ways to make small molecules, tryptorubin A posed a more direct challenge: how to develop a set of organic chemistry reactions to make this natural compound with its highly strained, spherical, cage-like shape.
They eventually found a method to do that, but in analyzing the product they discovered that it existed in two alternative shapes, which they eventually recognized as roughly right side in and inside out. That type of isomerism has been considered impossible except in larger molecules that can fold into complex shapes with much less strain.
The discovery posed a new challenge: how to synthesize just the natural isomer of tryptorubin A, or alternatively the inside-out isomer. The solution that Reisberg and colleagues devised was to install a cluster of chemical bonds at the start of the synthetic process so as to force the structure to bend in one way or the other and then remove that guiding element once the structure closed on itself.
As chemists our job is to control the shapes of molecules in ever more sensitive ways to make better drugs and other products, Reisberg says. Here, we've shown that we can do that in a complex and unexpected context that may be pertinent for the development of some future drugs.
Total synthesis reveals atypical atropisomerism in a small-molecule natural product, tryptorubin A was written by Solomon Reisberg, Yang Gao, and Phil Baran, of Scripps Research; and Allison Walker, Eric Helfrich, and Jon Clardy of Harvard Medical School.
Funding was provided by the National Institutes of Health (GM-118176, R01AT009874).
Chemistry Baran, Phil
Most recent headlines
06/10/2025
France T l visions, France's leading broadcaster, has received the 2025 EBU ...
04/09/2025
Monumental Sports & Entertainment (MSE), in collaboration with Dalet, has been a...
30/08/2025
WASHINGTON The Federal Communications Commission has adopted its FY 2025 Regulatory Fees Order that establishes the regulatory fee rates for the broadcast stati...
29/08/2025
Australian Red Cross and SBS launch training to help workplaces in the fight aga...
29/08/2025
The National Film and Video Foundation (NFVF), an agency of the Department of Sp...
29/08/2025
L3Harris Technologies has concentrated decades of expertise across the entire enterprise to develop affordable and reliable best-of-breed solutions to rapidly c...
29/08/2025
BURBANK, Calif. The CW Network and the Pac-12 Conference have announced a new media rights deal that will extend their broadcast partnership beginning with the ...
29/08/2025
NEW YORK Gracenote has released a new analysis of its global video dataset showing that the number of FAST channels grew nearly 14% from Q1 2025 and 76% since 2...
29/08/2025
SAN JOSE, Calif. Harmonic has announced a series of improvements to its live sports streaming solution that the company said will improve fan engagement, protec...
29/08/2025
NEW YORK and LOS ANGELES Fox Corp. and YouTube TV last night announced a renewal of the full portfolio of Fox networks, including Fox News Channel, Fox Business...
29/08/2025
Budapest, Hungary, August 2025 - The integration of Microsoft Teams Rooms (MTR) with Lightware's Taurus universal matrix switchers delivers a new level of f...
29/08/2025
Frequency, the engine behind many of the world's best-known streaming television channels, today announced it will launch Studio Live, a next-generation uni...
29/08/2025
In an era when AI and cyber resilience are essential, Scality will mark the 10th anniversary of Scality Day on October 16, 2025 in Paris. This flagship global e...
29/08/2025
Disguise's In-House Creative and Technical Teams Pre-Visualised, Programmed and Delivered Content for the Experience, All Powered by EX 3+
Technology solu...
29/08/2025
Disguise will be demonstrating the latest workflows for TV, film and live events on a number of partner booths at the show
Disguise, the industry-leading tech...
29/08/2025
STOCKHOLM, Sweden Accedo will showcase Accedo Compose, its AI agent-powered modular orchestration layer that assists streaming providers in transitioning client...
29/08/2025
LOS ANGELES Cineverse has announced that it is working with Xperi to bring four of its streaming channels to automobiles for the first time as part of the DTS A...
29/08/2025
DALLAS & ATLANTA Gray Media has announced an agreement with the sports streaming service Victory+ to simulcast 17 Dallas Stars NHL games in 15 television market...
29/08/2025
NEW YORK AND CULVER CITY Comcast NBCUniversal and Amazon have announced new and extended distribution agreements that will expand the content available on their...
29/08/2025
FOOTHILL RANCH, Calif. RED Digital Cinema will feature its Cine-Broadcast Module supporting live broadcast workflows during IBC2025, Sept. 12-15, at the RAI Ams...
29/08/2025
29 Aug 2025
Kyivstar Rings Opening Bell at Nasdaq Marking Landmark Listing and ...
29/08/2025
More than half of all NFL games live on Sky for the first timeFriday 29 August 2025
Sky Sports has announced a new three-year deal with the NFL, extending its ...
29/08/2025
Back to All News
RIV4LRIES: The Trailer of the New Series With Samuele Carrino ...
29/08/2025
Get ready for an inspiring and emotional insight into the world of competitive Irish dancing with My Story: Tomi Champion of the World airing on RT 2 this monda...
29/08/2025
RT has today announced that David McCullagh is to be the new presenter of RT Radio 1's flagship Today programme, which airs every weekday at 10am, replaci...
28/08/2025
By Kristin Feeley, Director, Documentary Film & Artist Programs
If you want to tell untold stories, if you want to give voice to the voiceless, you've got ...
28/08/2025
Directed by Steven Bognar and Julia Reichert, Sundance Institute-supported Amer...
28/08/2025
Corridos have been a cornerstone of M sica Mexicana for generations, telling stories rooted in everyday life. Now, a new chapter is taking shape: motivational c...
28/08/2025
Los corridos han sido un pilar de la M sica Mexicana durante generaciones, contando historias enraizadas en la vida cotidiana. Ahora, un nuevo cap tulo est tom...
28/08/2025
Earlier this month, we promised our Verano Forever party would bring the heat, a...
28/08/2025
L3Harris will provide the Polish F-16V fleet with the Viper Shield electronic warfare system as part of an upgrade program....
28/08/2025
Bilbao, August 26, 2025 - AgileTV, an international television and video technol...
28/08/2025
Ken Wilkinson is an Emmy Awards nominated New York audio engineer who specialises in production sound mixing for film, commercial, episodic and documentary work...
28/08/2025
NEW YORK FuboTV today announced that it will launch Fubo Sports, a skinny bundle that focuses on sports with a subscription price of $56 monthly....
28/08/2025
NEVADA City, Calif. At IBC2025, Sept. 12-15 at the RAI Amsterdam, Telestream will debut its new Global Ingest strategy, introducing a next-generation ingest arc...
28/08/2025
Dr. Rhoda Bernard Releases Groundbreaking Debut Book on Accessible Arts Educatio...
28/08/2025
TAG Video Systems, the leader in software-based IP end-to-end workflow monitoring, deep probing, and real-time visualization, has named Oliver Gappa as Sales Di...
28/08/2025
AI-based voice enhancement will be among a series of innovations making their IBC 2025 debut on the DHD stand B46 in Hall 8 at the RAI Amsterdam Convention Cent...
28/08/2025
Telef nica Servicios Audiovisuales (TSA), the leading system integrator and service provider in the media sector in Spain, with the support of Appear, the globa...
28/08/2025
To fully immerse sailing fans in the world's biggest offshore yacht race, production company, Optical Media turned to LiveU's On-site Production solutio...
28/08/2025
Working with Calrec on its most recent overhaul, radio and television broadcaster, WNED has migrated to a fully IP infrastructure with multiple Type R consoles,...
28/08/2025
Cleeng, the Subscriber Retention Management (SRM ) inventor, has unveiled Cleeng Pro, the first-ever direct-to-consumer (D2C) subscription management platform t...
28/08/2025
Zixi, the industry leader in live broadcast-quality video over IP, today announced that French media distribution platform OKAST has selected Zixi to enable rel...
28/08/2025
Solution offers a streamlined, speaker-free architecture to optimize integration with premium external loudspeakers and advanced loudness metering
Nixer Pro Au...
28/08/2025
Cinegy, the premier provider of software-defined television technology, has announced a strategic partnership with Vision One Touch Film Production Services L.L...
28/08/2025
Telestream, a global leader in media workflow technologies, will debut its new Global Ingest strategy at IBC2025, introducing a next-generation ingest architect...
28/08/2025
Tier 1 operator selects Broadpeak to power high-performance, unified CDN solution across Norway, Sweden and Finland
Broadpeak, a leader in streaming and moneti...
28/08/2025
Leading video software provider, Synamedia, today announced that 24 Frames Digital, one of India's leading live event streaming service providers, has chose...
28/08/2025
Meet VisualOn at IBC2025: See What's Next in AI-Powered Video Streaming Join VisualOn at IBC2025 and discover how our AI-driven Optimizer and advanced media...
A new kind of molecular differentness Chemists' discovery of a small bacterial molecule with natural and inside-out' versions could have implications for future drug development
