Use of triethylene glycol to mimic oligosaccharides: design and synthesis of a ligand based on chromomycin A3.
Chromomycin A3 (CRA3) is an antitumor antibiotic that binds to DNA. It contains an acac-like metal binding site and forms a 2:1 complex with Mg2+. Interestingly, acac ligands similar to CRA3 form 1:1 complexes with Mg2+. We have previously shown that the unusual stability of the 2:1 CRA3-Mg2+ complex is related to a favorable intermolecular interaction between the CDE trisaccharide of one CRA3 molecule and the chromophore of the other. We have used this knowledge to design and synthesize a very simple molecule in which a triethylene glycol chain mimics the CDE trisaccharide of CRA3. This minimalist ligand behaves like CRA3 with respect to dimer formation. This result sheds light on how the CRA3 sugars function to stabilize the dimer. At the same time, the work provides a starting point for investigating the relationship between dimer formation and DNA binding. Starting from these relatively simple metal complexes, it should be possible to develop a better understanding of the structural requirements for DNA binding by CRA3 and related molecules.
Silva
D J
DJ
Department of Chemistry, Princeton University, New Jersey 08544, USA.
Kraml
C M
CM
Kahne
D
D
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D002240:Carbohydrate Sequence; D014128:Chromomycin A3 / Q000737:chemistry* / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D008024:Ligands; D008274:Magnesium / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D013053:Spectrophotometry
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D008024:Ligands; D009844:Oligosaccharides; C028914:triethylene glycol; D011092:Polyethylene Glycols; D004247:DNA; D014128:Chromomycin A3; D008274:Magnesium