thiopeptides; ultrafast spectroscopy; circular dichroism; conformational dynamics; exciton coupling; peptide structure
Oppermann Malte, Spekowius Jasmin, Bauer Benjamin, Pfister Rolf, Chergui Majed, Helbing Jan (2019), Broad-Band Ultraviolet CD Spectroscopy of Ultrafast Peptide Backbone Conformational Dynamics, in The Journal of Physical Chemistry Letters
, 10(11), 2700-2705.
Oppermann Malte, Bauer Benjamin, Rossi Thomas, Zinna Francesco, Helbing Jan, Lacour Jérôme, Chergui Majed (2019), Ultrafast broadband circular dichroism in the deep ultraviolet, in Optica
, 6(1), 56-56.
The desire to obtain site-specific information during folding, conformational transitions, solvation or signal transduction in biopolymers has produced a library of spectroscopic labels for equilibrium and photo-triggered experiments. Prominent examples are fluorescence markers and quenchers, which make it possible to investigate distance and orientation fluctuations down to the single molecule level. To follow dynamics on a (sub)-nanosecond timescale, on the other hand, detecting spontaneous fluorescence is usually not sufficient and faster probing methods are needed. Time-resolved infrared spectroscopy, for example, is sensitive to picosecond dynamics, which it can interrogate locally via site-specific vibrational modes. Suitable IR-transitions can be created by isotope labelling or by introducing specific IR-labels, which exhibit infrared bands in spectral regions not contaminated by the bulk molecule or the solvent. Interactions between adjacent labels (coupling, energy transfer) and the relative orientation of their transition dipole moments can even provide direct structural information. In this context we have also attempted in recent years to introduce transient vibrational circular dichroism as a new probe of local structural change.The downside of vibrational probes is that transition dipole moments are usually small and couplings rather weak and of short range. This is very different for electronic transitions in the UV, which are, on the other hand, much more difficult to localize within specific molecular units. Sparsely occurring amino acid residues with aromatic side chains like Tryptophan are one exception, and they have already served as local probes for ultrafast energy and charge transfer in proteins. Here we propose to use thio-substituted amino acids, which directly “label” the backbone of a polypeptide or protein by red-shifting its strong pi-pi* transition from 200 nm to 270 nm. In the past, we photo-triggered conformational change in small peptides by cis-trans isomerization of the thiopeptide bond. In the meantime, methods have been developed by which thioamide bonds can be introduced at various positions in much larger proteins. In addition, multidimensional spectroscopies have been extended into the deep UV-range. In this project we intend to combine non-linear spectroscopy and the site-specific UV absorption and circular dichroism of single and multiple interacting thioamide labels to develop new probes for conformational changes and structure fluctuations in peptides.