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We describe the use of Co(III) Schiff base–DNA conjugates, a versatile class of research tools that target C2H2 transcription factors, to inhibit the Hedgehog (Hh) pathway. In developing mammalian embryos, Hh signaling is critical for the formation and development of many tissues and organs. Inappropriate activation of the Hedgehog (Hh) pathway has been implicated in a variety of cancers including medulloblastomas and basal cell carcinomas. It is well-known that Hh regulates the activity of the Gli family of C2H2 zinc finger transcription factors in mammals. In Drosophila the function of the Gli proteins is performed by a single transcription factor with an identical DNA binding consensus sequence, Cubitus Interruptus (Ci). We have demonstrated previously that conjugation of a specific 17 base-pair oligonucleotide to a Co(III) Schiff base complex results in a targeted inhibitor of the Snail family C2H2 zinc finger transcription factors. Modification of the oligonucleotide sequence in the Co(III) Schiff ba...
| Authors: | Ryan R. Hurtado; Allison S. Harney; Marie C. Heffern; Robert J. Holbrook; Robert A. Holmgren; Thomas J. Meade | |
| Journal: | Molecular Pharmaceutics | |
| Year: | 2012 | |
| DOI: | 10.1021/mp2005577 | |
| Publication date: | 20-01-2012 |
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