לוח שנה משולב

RECENT ADVANCES IN AUTOMATED OLIGOSACCHARIDE AND GLYCOPEPTIDE SYNTHESIS

Mattan Hurevich,a and Peter H. Seeberger.a,b

aDepartment of Biomolecular Systems, Max-Planck-Institute of Colloids and Interfaces, Am Mühlenberg 1, 14476 Potsdam-Golm,Germany and bFreie Universität Berlin, Institute of Chemistry and Biochemistry, Arnimallee 22, 14195 Berlin, Germany.

The automated solid-phase synthesis of oligopeptides and oligonucleotides had an immense impact on biochemical research and has fulfilled the growing demand of the scientific community to study short biopolymers and their biological, biophysical and mechanical characteristics.
There is a major interest in developing robust methods for the synthesis of glycopeptides and oligosaccharides as their chemical synthesis requires compatible solutions for challenges associate with glycan assembly. The quest for solid phase strategy suitable for oligosaccharide and glycopeptide synthesis is still in the critical and stimulating stage of continuous development.
Automated solid-phase oligosaccharide synthesis has been developed to provide ready to use complex carbohydrates to the research community.1 Many important chemical and technological milestones have been achieved in the process of creating a reliable automated oligosaccharide synthesis system.
The developments in the automated solid-phase synthesis of oligosaccharides emphasize the contribution of adjacent fields such as NMR and flow chemistry to carbohydrate synthesis.
The synthesis of sialosides,2 arabinofuranosides,3 polymannosides, and glycopeptides4 using automated solid phase platform will be presented. This study demonstrates that the new generation of oligosaccharide synthesizers overcome many technical and chemical hurdles and simplifies the synthesis of ready to conjugate oligosaccharides5 and glycopeptides.

References:
[1] Plante, O. J.; Palmacci, E. R.; Seeberger, P. H. Science 2001, 291, 1523-1527; Calin, O.; Eller, S.; Seeberger, P.H. 2013 Angew. Chem Int. Ed, 2013, 52, 5862-5865
[2] Esposito, D.; Hurevich, M.; Castagner, B.; Wang, C. C.; Seeberger, P. H. Beilstein J. Org. Chem. 2012, 8, 1601-1609.
[3] Kandasamy, J.; Hurevich, M.; Seeberger, P. H. Chem. Commun., 2013, 49, 4453-4455.
[4] Hurevich, M.; Seeberger, P. H. Chem. Commun., 2014, 50, 1851-1853.
[5] Krock, L.; Esposito, D.; Castagner, B.; Wang, C. C.; Bindschadler, P.; Seeberger, P. H. Chem. Sci. 2012, 3, 1617-1622.

I will discuss data from a series of monkey fMRI experiments showing evidence for a reward induced spatially-selective modulation of visual cortical activity. These effects reflect a dopamine-dependent reward-prediction error signal that may be caused by ventral mid-brain nuclei. I will also discuss data from our first microstimulation experiments in the monkey targeting the ventral midbrain which revealed profound functional network changes in the reward circuitry and changes in behavior during a free choice task in monkeys.

Imaging Flow Cytometry combines speed, sensitivity, and phenotyping abilities found in flow cytometry with the detailed imagery and functional insight of microscopy, for an extensive range of novel applications. It allows quantitating cellular morphology and the intensity and location of fluorescent probes on, in, or between cells, even in rare sub-populations and highly heterogeneous samples. We will present here several examples of the projects done with the ImageStreamX. The wide range of applications used include studying intracellular localization, shape changes and morphology, co-localization, cell signaling, T cell - APC interactions, DNA damage and repair, nuclear translocation, cell death and apoptosis, phagocytosis and internalization, FISH, vesicle trafficking, and many others.