CHED 1328 |
| Aureolic acid antibiotics,Chromomycin A3 (CHR) and Mithramycin (MTR), supposedly inhibit transcription via reversible association with DNA. Presence of a divalent metal ion is an absolute requirement for DNA binding. They alone bind bivalent cation such as Mg2+ and Zn2+ to form (antibiotic):metal ion complexes. We have examined the effect of MTR/CHR on the structure and function of potential targets like Zn(II)-dependent alcohol dehydrogenase (ADH) and alkaline phosphatase (AP). Pre-incubation of ADH with MTR/CHR leads to inhibition of enzymatic activity in a non-competitive way with inhibitory constant in the micromolar order. Dynamic light scattering, isothermal titration calorimetry and differential scanning calorimetry studies have shown that the antibiotic(s) disrupt the oligomeric structure of the enzymes via specific association with Zn(II) at the structural and catalytic sites. Results from Confocal microscopy indicate the co-localization of the antibiotic and ADH in HepG2 cells, thereby validating the possibility of interaction under in vivo condition. The results imply that Zn(II)- proteins could be an additional target of the antibiotics. |
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Undergraduate Research Poster Session: Medicinal Chemistry
2:00 PM-4:00 PM, Monday, April 7, 2008 Morial Convention Center -- Hall A, Poster
Division of Chemical Education |