Open AccessTriostin A Derived Cyclopeptide as Architectural Template for the Alignment of Four Recognition Units
Author(s) -
Kotyrba Ursula M.,
Pröpper Kevin,
Sachs Eike-F.,
Myanovska Anastasiya,
Joppe Tobias,
Lissy Friederike,
Sheldrick George M.,
Koszinowski Konrad,
Diederichsen Ulf
Publication year - 2014
Publication title -
chemistryopen
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.644
H-Index - 29
ISSN - 2191-1363
DOI - 10.1002/open.201400001
Subject(s) - nucleobase , chemistry , microscale thermophoresis , tandem , combinatorial chemistry , dna , stereochemistry , biochemistry , materials science , composite material
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.