New technique enables spatial separation of peptide structures

November 6, 2018, Helmholtz Association of German Research Centres
Different 3-D structures of biological molecules, for example a dipeptide with two distinct conformations shown as red and blue, can be spatially separated by shooting a cold molecular beam through a strong electric field. The separated structures can then be investigated and imaged individually. Credit: Nicole Teschmit

A team of scientists at DESY and Universität Hamburg has reached another milestone towards the direct imaging of individual biomolecules: the group led by Jochen Küpper from the Center for Free-Electron Laser Science developed a new experimental technique which enables the separation of different peptide structures in order to analyze and image them separately. The scientists report their method, which ultimately can be applied in diverse experiments, in the scientific journal Angewandte Chemie International Edition.

Peptides are a kind of short version of proteins, the workhorses of life. Proteins cover a wide variety of functions in the organism: They regulate the functionality of living cells and are responsible, for example, for the reproduction of cells or the transport of oxygen. This wide-ranging functionality is enabled by their unique 3-dimensional . Changes in this structure can dramatically alter protein function, potentially even leading to severe diseases. The 3-dimensional protein structure is not only determined by the sequence of amino acids, but also by intra-molecular interactions such as hydrogen bonding between different parts of the molecule.

A current method to study such interactions in detail is to study isolated small peptides, that is chains of single amino acids, in the . However, even single amino acids and small peptides can arrange themselves into different 3-dimensional structures, so called conformers. This fact makes a detailed analysis of these important biomolecular building blocks rather complicated, since techniques such as X-ray diffraction require identical 3-dimensional structures to produce structural data at atomic resolution.

"Our aim therefore was to develop new experimental techniques that produce peptide samples in the gas phase with identical 3-dimensional structures," says Nicole Teschmit from the cluster of excellence CUI (Centre for Ultrafast Imaging) at Universität Hamburg, first author of the study. The team used laser desorption to produce very cold molecular beams of intact dipeptide molecules, which were then identified by laser spectroscopy. At minus 271 degrees Celsius, the different conformers no longer interconvert in such a cold molecular beam. To spatially separate the different structures, the scientists used strong electric fields that interact with the specific dipole moments of the different conformers and deflect them to different extends. With this method the scientists now succeeded in completely spatially separating the two conformers of the prototypical dipeptide Ac-Phe-Cys-NH2 and producing pure samples of either conformer in the gas phase.

"We succeeded for the first time in demonstrating cold molecular beams of conformer-selected peptides. Such samples will enable the analysis of conformer-specific processes with general techniques which usually cannot differentiate between structures," co-author Daniel Horke says. Furthermore, the low temperatures of the generated molecular ensembles allow for strongly fixing the molecules in space. This is a prerequisite for the recording of atomically resolved images of biomolecules, as Küpper points out: "Our method is a milestone on the road toward a direct structural imaging of biological molecules."

Explore further: Reaction rate of many molecules depends on their shape

More information: Nicole Teschmit et al. Spatially Separating the Conformers of a Dipeptide, Angewandte Chemie International Edition (2018). DOI: 10.1002/anie.201807646

Related Stories

Reaction rate of many molecules depends on their shape

October 3, 2013

Most molecules occur in several shapes, which may behave very differently. Using a sorting machine for molecules, a German–Swiss research team can now for the first time directly measure the various reaction rates of different ...

A new dimension for 3-D protein structures

May 13, 2013

( —3D structures of biological molecules like proteins directly affect the way they behave in our bodies. EPFL scientists have developed a new infrared-UV laser method to more accurately determine the structure ...

Molecular Lego with an encoded blueprint

March 3, 2016

Nature contains a special kind of Lego brick: biological molecules, peptides to be exact, that can be built together to form a wide range of complex structures. Unlike the popular toy bricks, however, the molecular building ...

Double-bridged peptides bind any disease target

April 30, 2018

Peptides are short chains of amino acids that can bind to proteins and change their function. They show high binding affinity, low toxicity, and are easy to synthesize, all of which makes peptides ideal for use in drug development, ...

Recommended for you

Matter waves and quantum splinters

March 25, 2019

Physicists in the United States, Austria and Brazil have shown that shaking ultracold Bose-Einstein condensates (BECs) can cause them to either divide into uniform segments or shatter into unpredictable splinters, depending ...

How tree diversity regulates invading forest pests

March 25, 2019

A national-scale study of U.S. forests found strong relationships between the diversity of native tree species and the number of nonnative pests that pose economic and ecological threats to the nation's forests.


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.