Discovery is expected to impact pharmaceutical and agricultural industries
Molecules containing carbon-halogen bonds are produced naturally across all kingdoms of life and constitute a large family of natural products with a broad range of biological activities. The presence of halogen substituents in many bioactive compounds has a profound influence on their molecular properties.
One of the Holy Grails in chemical science has been to find the late-stage, site-specific incorporation of a halogen atom into a complex natural product by replacing an sp³ C-H bond (one of the most inert chemical bonds known in an organic compound) with a C-X bond (X=halogen). Until work was undertaken in the laboratory of Xinyu Liu at the University of Pittsburgh, there was no reliable synthetic or biological method known to be able to achieve this type of transformation.
In an article published online on Sept. 14 in Nature Chemical Biology, the group, led by Liu, an assistant professor of chemistry within Pitt's Kenneth P. Dietrich School of Arts and Sciences, has discovered the first enzyme that can accomplish this feat.
Liu and postdoctoral fellow Matthew Hillwig studied bacteria and demonstrated that the WelO5 protein is the first enzyme identified to have the capacity to mediate the regio- and stereospecific replacement of an aliphatic C-H bond to C-Cl bond on a freestanding small molecule. Specifically, they determined this by studying the biogenesis of hapalindole-type alkaloid welwitindolinones in stigonematalean cyanobacteria.
Their work also provides conclusive evidence on a longstanding question regarding the enzymatic origin of chlorine substitution in the biogenesis of hapalindole-type alkaloids in accordance with a proposal that was recently formulated by the Liu group.
It is expected that this discovery will present unprecedented opportunities to evolve new catalysts for selective late-stage halogenations on unactivated carbons in complex molecular scaffolds.
This development could find broad applications in pharmaceutical and agricultural industries, enabling medicinal chemists to tailor synthetic molecules with halogen substituents in order to improve their pharmacological profiles.
Joe Miksch | Eurek Alert!
Newly designed molecule binds nitrogen
23.02.2018 | Julius-Maximilians-Universität Würzburg
Atomic Design by Water
23.02.2018 | Max-Planck-Institut für Eisenforschung GmbH
A newly developed laser technology has enabled physicists in the Laboratory for Attosecond Physics (jointly run by LMU Munich and the Max Planck Institute of Quantum Optics) to generate attosecond bursts of high-energy photons of unprecedented intensity. This has made it possible to observe the interaction of multiple photons in a single such pulse with electrons in the inner orbital shell of an atom.
In order to observe the ultrafast electron motion in the inner shells of atoms with short light pulses, the pulses must not only be ultrashort, but very...
A group of researchers led by Andrea Cavalleri at the Max Planck Institute for Structure and Dynamics of Matter (MPSD) in Hamburg has demonstrated a new method enabling precise measurements of the interatomic forces that hold crystalline solids together. The paper Probing the Interatomic Potential of Solids by Strong-Field Nonlinear Phononics, published online in Nature, explains how a terahertz-frequency laser pulse can drive very large deformations of the crystal.
By measuring the highly unusual atomic trajectories under extreme electromagnetic transients, the MPSD group could reconstruct how rigid the atomic bonds are...
Quantum computers may one day solve algorithmic problems which even the biggest supercomputers today can’t manage. But how do you test a quantum computer to...
For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.
In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...
Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale
Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...
15.02.2018 | Event News
13.02.2018 | Event News
12.02.2018 | Event News
23.02.2018 | Physics and Astronomy
23.02.2018 | Health and Medicine
23.02.2018 | Physics and Astronomy