Triostin A Derived Cyclopeptide as Architectural Template for the Alignment of Four Recognition Units |
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| Authors: | Ursula M Kotyrba Kevin Pr?pper Eike-F Sachs Anastasiya Myanovska Tobias Joppe Friederike Lissy George M Sheldrick Konrad Koszinowski Ulf Diederichsen |
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| Affiliation: | [a]Institute of Organic and Biomolecular Chemistry, Georg-August-University Göttingen, Tammannstrasse 2, 37077 Göttingen (Germany), E-mail: ;[b]Institute of Inorganic Chemistry, Georg-August-University Göttingen, Tammannstrasse 4, 37077 Göttingen (Germany) |
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| Abstract: | The DNA bisintercalator triostin A is structurally based on a disulfide-bridged depsipeptide scaffold that provides preorganization of two quinoxaline units in 10.5 Å distance. Triostin A analogues are synthesized with nucleobase recognition units replacing the quinoxalines and containing two additional recognition units in between. Thus, four nucleobase recognition units are organized on a rigid template, well suited for DNA double strand interactions. The new tetra-nucleobase binders are synthesized as aza-TANDEM derivatives lacking the N-methylation of triostin A and based on a cyclopeptide backbone. Synthesis of two tetra-nucleobase aza-TANDEM derivatives is established, DNA interaction analyzed by microscale thermophoresis, cytotoxic activity studied and a nucleobase sequence dependent self-aggregation investigated by mass spectrometry. |
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| Keywords: | ESI mass spectrometry microscale thermophoreses nucleobase recognition peptide nucleic acids triostin A structure characterization of biomolecules |
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