Featured Research

from universities, journals, and other organizations

A new method for clicking molecules together

Date:
July 22, 2013
Source:
Ecole Polytechnique Fédérale de Lausanne
Summary:
Scientists have developed a quick and simple method for connecting and assembling new molecules together, paving a new road for synthetic chemistry, material science, chemical biology, and even drug discovery.

Thiols are sulfur-containing molecules found in most proteins of the human body. Characterized by their 'garlicky' smell, they also give coffee, sweat and the spray of skunks their unique odor. Because they are so widespread in biology, medicine and materials science, thiols are ideal targets for connecting molecules like drugs or polymers together, except that they must first be fitted with a chemical group that acts like an adaptor to other molecules.

One of the most potentially useful of these 'adaptors' are the alkynes, which can be extremely powerful in bioconjugation. The problem is that adding alkynes to thiols ('alkynylation') has been too difficult to be of any use outside the lab. But now, in a patent-pending publication in the Journal of the American Chemical Society, EPFL scientists have found a way to make the connection in five minutes and at room temperature, paving the way to commercial, medical and perhaps industrial applications.

Thiol alkynylation is part of 'modular' or 'click' chemistry, a field that has far-reaching applications in drug discovery, nanotechnology and bioengineering. The idea is to synthesize large molecules by quickly "clicking together" smaller ones, allowing us to change previously-inaccessible complex molecules. Although relatively new, click chemistry is actually inspired by natural processes. For example, after being synthesized in the cell, proteins are further modified with carbohydrates and lipids to change their properties. This process, known as post-translational modification, involves a whole host of complex enzymes that can be sidestepped in the lab by using click chemistry methods.

In order to achieve alkynylation, researchers from the group of Jerôme Waser at EPFL used an alkyne-transfer reagent called TIPS-ethynyl-benziodoxolone (TIPS-EBX), which they have made commercially available by collaborating with Sigma-Aldrich. The EPFL researchers had found that previous alkynylation reactions were limited by slow reaction rates and also needed a relatively unstable gold catalyst. By using TIPS-EBX, the researchers found that they were able to alkynylate thiols with very short reaction times and without having to use any metal catalyst.

TIPS-EBX is a highly reactive microcrystalline powder (like sugar) that is stirred in a liquid to make a solution. When the solution was mixed in with alkynes and thiols, it proved to be excellent in 'clicking' them together. Because of its structure, TIPS-EBX is also considerably more stable than previous alkynylation reagents. But the real benefit for Waser's group was that TIPS-EBX allowed them to carry out the thiol alkynylation reactions within five minutes, at room temperature (23oC) and in open-flask conditions, meaning that this previously challenging transformation can now be performed quickly, safely and under normal conditions.

Thiols are important building blocks in the synthesis of natural, pharmaceutical and medicinal products, but they also contain chemical components which could obstruct the alkynylation reaction. To confirm their new alkynylation method, Waser's group tested it on a range of thiols that contained the most common and reactive chemical groups present in bioactive molecules. Of the 35 thiols tested, 29 produced yield above 92%, confirming that the TIPS-EBX reaction can be applied across a wide range of thiols -- even those in human proteins, which is expected to impact biotechnology as we know it. Waser says: "Introducing an alkyne into thiol-containing molecules allows to further modify them in order to make future bioconjugates."

The breakthrough has enormous implications for chemical biology, drug design and materials science, and the researchers have even filed a patent on the method. Following their success with alkynylating a cysteine amino acid, the group is now testing their method on actual proteins, attempting to change their properties by modifying associated molecules like lipids, glucose derivatives and even synthetic polymers.


Story Source:

The above story is based on materials provided by Ecole Polytechnique Fédérale de Lausanne. Note: Materials may be edited for content and length.


Journal Reference:

  1. Marcel Reiners, Ke Xu, Nabeel Aslam, Anjana Devi, Susanne Hoffmann-Eifert, Rainer Waser. Study of the Growth and Crystallization of TiO2 Thin Films by ALD using a Novel Amido Guanidinate Titanium Source and Tetrakis-dimethylamido-titanium. Chemistry of Materials, 2013; 130702155346007 DOI: 10.1021/cm303703r

Cite This Page:

Ecole Polytechnique Fédérale de Lausanne. "A new method for clicking molecules together." ScienceDaily. ScienceDaily, 22 July 2013. <www.sciencedaily.com/releases/2013/07/130722111426.htm>.
Ecole Polytechnique Fédérale de Lausanne. (2013, July 22). A new method for clicking molecules together. ScienceDaily. Retrieved September 20, 2014 from www.sciencedaily.com/releases/2013/07/130722111426.htm
Ecole Polytechnique Fédérale de Lausanne. "A new method for clicking molecules together." ScienceDaily. www.sciencedaily.com/releases/2013/07/130722111426.htm (accessed September 20, 2014).

Share This



More Matter & Energy News

Saturday, September 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

MIT BioSuit A New Take On Traditional Spacesuits

MIT BioSuit A New Take On Traditional Spacesuits

Newsy (Sep. 19, 2014) — The MIT BioSuit could be an alternative to big, bulky traditional spacesuits, but the concept needs some work. Video provided by Newsy
Powered by NewsLook.com
Virtual Reality Headsets Unveiled at Tokyo Game Show

Virtual Reality Headsets Unveiled at Tokyo Game Show

AFP (Sep. 18, 2014) — Several companies unveiled virtual reality headsets at the Tokyo Game Show, Asia's largest digital entertainment exhibition. Duration: 00:48 Video provided by AFP
Powered by NewsLook.com
Apple's iOS8 Includes New 'Killswitch' To Curb Theft

Apple's iOS8 Includes New 'Killswitch' To Curb Theft

Newsy (Sep. 18, 2014) — Apple's new operating system, iOS 8, comes with Apple's killswitch feature already activated, unlike all the models before it. Video provided by Newsy
Powered by NewsLook.com
Stocks Hit All-Time High as Fed Holds Steady

Stocks Hit All-Time High as Fed Holds Steady

AP (Sep. 17, 2014) — The Federal Reserve signaled Wednesday that it plans to keep a key interest rate at a record low because a broad range of U.S. economic measures remain subpar. Stocks hit an all-time high on the news. (Sept. 17) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins