Book of Abstracts - Ruhr-Universität Bochum

P-38
ISBOMC `10 5.7 – 9.7. 2010 Ruhr-Universität Bochum
Bioorthogonal Coupling Strategies in the Synthesis of CORM-peptide Conjugates
a
Hendrik Pfeiffer, a Johanna Niesel, b and Ulrich Schatzschneider* a
Ruhr-Universität Bochum, Department of Chemistry and Biochemistry,
Universitätsstrasse 150, 44801 Bochum, Germany, hendrik.pfeiffer@rub.de
In the human body carbon monoxide possesses versatile properties as a signalling mediator and
participates in important biological processes. Beside being a potent vasodilator, CO can exert antiinflammatory,
anti-apoptotic, and anti-proliferative effects. 1,2 Since it is a toxic gas and difficult to
handle, there is considerable interest in the development of CO releasing molecules (CORMs) as
"solid storage forms" for carbon monoxide. Therefore, transition metal carbonyl complexes are highly
interesting target structures. 3 Compared to thermally induced liberation of CO, photoactivated CO
release will allow for a precise spatial and temporal control of its biological action. 4 We have recently
synthesized several tungsten, molybdenum, and manganese complexes with bidentate as well as
tridentate nitrogen donor ligands as promising new photoCORMs, which are inert in the dark in
aqueous solution, but release CO upon irradiation. 5
Carrier peptides are important vehicles to achieve accumulation of bioactive cargos in specific
biological target sites. Thus, we have explored the functionalization of the parent photoCORMs with
model peptides using bioorthogonal coupling strategies, such as oxime ligation, Sonogashira crosscoupling,
or the alkyne-azide 1,3-dipolar cycloaddition (click reaction). 6
References
1. S. W. Ryter, J. Alam, A. M. K. Choi, Physiol. Rev. 2006, 86, 583-650.
2. T. R. Johnson, B. E. Mann, J. E. Clark, R. Foresti, C. J. Green, R. Motterlini, Angew. Chem. Int. Ed.
2003, 42, 3722-3729.
3. J. Boczkowski, J. J. Poderoso, R. Motterlini, Trends Biochem. Sci 2006, 31, 614-621.
4. U. Schatzschneider, Eur. J. Inorg. Chem. 2010, 1451-1467.
5. J. Niesel, A. Pinto, H. W. Peindy N'Dongo, K. Merz, I. Ott, R. Gust, U. Schatzschneider, Chem.
Commun. 2008, 1798-1800.
6. H. Pfeiffer, A. Rojas, J. Niesel, U. Schatzschneider, Dalton Trans. 2009, 4292-4298.
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