Volume 11 Supplement 1
New vitamin B12 derivatives activates sGC
© Gryko and Martin; licensee BioMed Central Ltd. 2011
Published: 1 August 2011
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 .
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”) .
This work was supported by the European Regional Found within the TEAM program, grant No. TEAM/2009-3/4.
- Ignarro LJ: Nitric oxide as a unique signaling molecule in the vascular system: a historical overview. J Physiol Pharmacol. 2002, 53: 503-514.PubMedGoogle Scholar
- Waldman SA, Sinacore MS, Lewicki JA, Chang LY, Murad F: Selective activation of particulate guanylate cyclase by a specific class of porphyrins. J Biol Chem. 1984, 259: 4038-4042.PubMedGoogle Scholar
- Petrus AK, Fairchild TJ, Doyle RP: Traveling the vitamin B12 pathway: oral delivery of protein and peptide drugs. Angew Chem Int Ed. 2009, 48: 1022-1028. 10.1002/anie.200800865.View ArticleGoogle Scholar
- Meldal M, Tornøe CW: Cu-catalyzed azide-alkyne cycloaddition. Chem Rev. 2008, 108: 2952-3015. 10.1021/cr0783479.View ArticlePubMedGoogle Scholar
- Iha RK, Wooley KL, Nystrom AM, Burke DJ, Kade MJ, Hawker CJ: Applications of orthogonal “click” chemistries in the synthesis of functional soft materials. Chem Rev. 2009, 109: 5620-5686. 10.1021/cr900138t.PubMed CentralView ArticlePubMedGoogle Scholar
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.