First-ever light-operated drug hones on most common target proteins

An international team of researchers has developed the first-ever light-controlled therapeutic agent whose effects focus specifically on the largest, most important class of drug target proteins—G protein-coupled receptors (GPCRs). The ability to control drug activity with light means that the therapeutic effects can be accurately delivered locally, thus reducing their effect on other areas and the resultant side effects, and helping to reduce the dosage required.

Related: Photo-switchable peptides promise precision control of drugs, and limited side effects

The research team was led by scientists in the Nanoprobes and Nanoswitches group of the Institute for Bioengineering of Catalonia (IBEC; Barcelona, Spain), and involved colleagues from the Institute of Advanced Chemistry of Catalonia (IQAC-CSIC), the Autonomous University of Barcelona (UAB), and the Bellvitge Biomedical Research Institute (IDIBELL), all in Barcelona, and the Institute for Functional Genomics (Montpellier, France).

The scientists developed Alloswitch-1, a small-molecule therapeutic agent that modulates drug target protein receptors specifically at the allosteric, or non-active, site of the protein. Allosteric modulators have a number of advantages over traditional drugs, offering higher selectivity of target receptors, tunable release according to whether the undesirable protein receptor activity is present, and lower potential for toxic effects.

Alloswitch-1 is the first light-controlled allosteric modulator of a G protein-coupled receptor (GPCR)
Alloswitch-1 is the first light-controlled allosteric modulator of a G protein-coupled receptor (GPCR). It is selective for the metabotropic glutamate receptor mGlu5 and enables the optical control of mGlu5 signaling in vivo.

“To build a photocontrolled modulator of a G protein-coupled receptor, we had to develop a new chemical design concept in which the photoswitch is not tethered to the drug but inserted within the pharmacophore, which is the group of atoms in the molecule of a drug responsible for its action,” explains Pau Gorostiza, group leader of IBEC’s Nanoprobes and Nanoswitches group. “We also got a bit lucky, because we not only obtained a photoswitchable GPCR ligand, but one of the most potent and selective allosteric modulators in its class.”

The effects of this ‘optopharmacological’ compound can be remotely controlled in space and time in living, wild-type organisms. This is an advantage over optogenetic manipulations, which require gene overexpression using viruses, for example.

Small molecule therapeutic agents such as Alloswitch-1, if they can be made available orally, could offer a competitive advantage over traditional drugs, which often affect off-target tissues and organs, leading to unwanted consequences and compromising their beneficial effects.

Full details of the work appear in the journal Nature Chemical Biology; for more information, please visit


Follow us on Twitter, 'like' us on Facebook, connect with us on Google+, and join our group on LinkedIn

Subscribe now to BioOptics World magazine; it's free!

Get All the BioOptics World News Delivered to Your Inbox

Subscribe to BioOptics World Magazine or email newsletter today at no cost and receive the latest news and information.

 Subscribe Now
Related Articles

New bioimaging technique offers clear view of nervous system

Scientists at Ludwig-Maximilians University have developed a technique for turning the body of a deceased rodent entirely transparent, revealing the central nervous system in unprecedented clarity....

Fluorescent jellyfish proteins light up unconventional laser

Safer lasers to map your cells could soon be in the offing -- all thanks to the humble jellyfish. Conventional lasers, like the pointer you might use to entertain your cat, produce light by emittin...

Eye test that pairs two in vivo imaging methods may detect Parkinson's earlier

A low-cost, noninvasive eye test pairs two in vivo imaging methods to help detect Parkinson's before clinical symptoms appear.

Fluorescence microscopy helps provide new insight into how cancer cells metastasize

By using fluorescence microscopy, scientists have discovered an alternate theory on how some cancer cells metastasize.


Neuro15 exhibitors meet exacting demands: Part 2

Increasingly, neuroscientists are working with researchers in disciplines such as chemistry and p...

Why be free?

A successful career contributed to keeping OpticalRayTracer—an optical design software program—fr...

LASER Munich 2015 is bio-bent

LASER World of Photonics 2015 included the European Conferences on Biomedical Optics among its si...

White Papers

Understanding Optical Filters

Optical filters can be used to attenuate or enhance an image, transmit or reflect specific wavele...

How can I find the right digital camera for my microscopy application?

Nowadays, image processing is found in a wide range of optical microscopy applications. Examples ...



Twitter- BioOptics World

Copyright © 2007-2016. PennWell Corporation, Tulsa, OK. All Rights Reserved.PRIVACY POLICY | TERMS AND CONDITIONS