DNA-Binding Cyclopeptides

DNA-Binding Cyclopeptides

Author: David Peralta

The cyclic peptide Triostin A, derived from Streptomyces triostinicus, is known to have potent antibacterial and antitumor activity because its quinoxaline side-chains can bisintercalate DNA. Triostin A can be modified to replace the quinoxalines with nucleobases that can be effective DNA major groove binders.

Ulf Diederichsen, Georg-August-University Göttingen, Germany, and colleagues synthesized Triostin A analogues with four nucleobase recognition units (ATTA or TTTT). The four recognition units were organized on a rigid template and were well-suited for DNA double strand interactions. These compounds, called aza-TANDEM derivatives, interacted with DNA double strands with the proper sequence complementarity and topological fitting. The purified compounds were then tested for self-aggregation and were shown to exhibit a median lethal dose (LD50) of >5 mg/mL in an Artemia salina assay.


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