Anti-Vitamins : new antibiotics / new anti-cancer drugs

Cancer and bacterial infections represent a big threat to modern society. Considering the significant rise of resistance to common antibiotic treatments, drugs with a new mode-of-action are urgently required. My laboratory develops antivitamin derivatives and bioconjugates as therapeutic agents.[1]
For the first time, an artificial B12 cofactor with a biomimetic peptide backbone (pB12, see below) is demonstrated to show reduced catalytic efficiencies in both the “base on" and “base off / his on” configurations both in vitro as well as in vivo.
B12 is used in bioconjugate-B12 derivatives to shuttle drug molecules selectively into cancer cells via the B12-uptake mechanism. In contrast, antivitamin B12 derivatives are designed to exhibit tight binding to B12-proteins.[2,3] As a direct con-sequence of enzyme inhibition, the antivitamins prevent the formation of tetrahydrofolate and thereby selectively suppress the replication of fast proliferating cancer cells.[2] We already succeeded in designing a new class of antivitamin B12 derivatives with an artificial peptide backbone and tunable coordination and redox properties.[3-5]

In vitro and in vivo studies with B12-dependent enzymes and bacteria demonstrated a promising inhibitory potential.[6] This research project with a medicinal orientation combines fundamental and applied research in the fields of organometallic chemistry and enzymology.

F. Zelder, Chem. Commun., 2015, 51(74), 14004.

[2] Peptide B12: emerging trends at the interface of inorganic chemistry, chemical biology and medicine
F. Zelder, K. Zhou and M. Sonnay, Dalton Trans., 2013, 42, 854.

K. Zelenka, H. Brandl, B. Spingler and F. Zelder, Dalton Trans., 2011, 40, 9665.

K. Zhou and F. Zelder, Angew. Chem. Int. Ed., 2010, 49, 5178.

F. H. Zelder, C. Buchwalder, R. M. Oetterli and R. Alberto, Chem. Eur. J., 2010, 16, 6155.

K. Zhou, R. Oetterli, H. Brandl, F. Lyatuu, W. Buckel and F. Zelder, ChemBioChem, 2012, 13, 2052.