Volume 11 Supplement 1

5th International Conference on cGMP: Generators, Effectors and Therapeutic Implications

Open Access

New vitamin B12 derivatives activates sGC

BMC Pharmacology201111(Suppl 1):P32

https://doi.org/10.1186/1471-2210-11-S1-P32

Published: 1 August 2011

Background

Protoporphyrin IX (PPIX) was shown to strongly activate in vitro the soluble guanylate cyclase enzyme (sGC), which makes it an interesting drug candidate for treatment of hypertension [1, 2]. In order to overcome the problem of PPIX poor bioavailability (especially in the case of oral administration), we decided to exploit the specific uptake pathway of vitamin B12, which was frequently used for delivering biologically active substances from the digestive system into the body cells. To this end, we embarked on the synthesis of a series of hybrid molecules, containing PPIX and vitamin B12 moieties, linked via chains of different length and chemical character [3].

Methods and results

Our synthetic approach is based on the synthesis of linking molecules containing a primary -NH2 group and -N3 or alkyne group at the other end. Amine functionality allows us to connect these linkers to vitamin B12, and to PPIX, finally, the union of the two parts is possible using Cu-catalyzed azide alkyne cycloaddition (the “click reaction”) [4].

Declarations

Acknowledgements

This work was supported by the European Regional Found within the TEAM program, grant No. TEAM/2009-3/4.

Authors’ Affiliations

(1)
Institute of Organic Chemistry Polish Academy of Sciences
(2)
University of Texas, Graduate School o Biomedical Science

References

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Copyright

© Gryko and Martin; licensee BioMed Central Ltd. 2011

This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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