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Triostin a derived cyclopeptide as architectural template for the alignment of four recognition units.

Kotyrba UM, Pröpper K, Sachs EF, Myanovska A, Joppe T, Lissy F, Sheldrick GM, Koszinowski K, Diederichsen U - ChemistryOpen (2014)

Bottom Line: 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.The new tetra-nucleobase binders are synthesized as aza-TANDEM derivatives lacking the N-methylation of triostin A and based on a cyclopeptide backbone.

View Article: PubMed Central - PubMed

Affiliation: Institute of Organic and Biomolecular Chemistry, Georg-August-University Göttingen Tammannstrasse 2, 37077 Göttingen (Germany) E-mail: udieder@gwdg.de.

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.

No MeSH data available.


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Structures of aza-TANDEM derivatives 1 (ATTA) and 2 (TTTT).
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fig02: Structures of aza-TANDEM derivatives 1 (ATTA) and 2 (TTTT).

Mentions: The additional nucleobases were introduced as peptoid building blocks replacing the native valines in the TANDEM backbone by N-alkylated glycine amino acids. Binding studies of tetra-nucleobase aza-TANDEM derivatives 1 (sequence ATTA) and 2 (sequence TTTT) (Figure 2) with DNA double strands performed by microscale thermophoresis indicate a sequence dependent recognition. For the tetra-thyminyl derivative 2 a potential for self-association and -aggregation was indicated by mass spectrometry.


Triostin a derived cyclopeptide as architectural template for the alignment of four recognition units.

Kotyrba UM, Pröpper K, Sachs EF, Myanovska A, Joppe T, Lissy F, Sheldrick GM, Koszinowski K, Diederichsen U - ChemistryOpen (2014)

Structures of aza-TANDEM derivatives 1 (ATTA) and 2 (TTTT).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4232271&req=5

fig02: Structures of aza-TANDEM derivatives 1 (ATTA) and 2 (TTTT).
Mentions: The additional nucleobases were introduced as peptoid building blocks replacing the native valines in the TANDEM backbone by N-alkylated glycine amino acids. Binding studies of tetra-nucleobase aza-TANDEM derivatives 1 (sequence ATTA) and 2 (sequence TTTT) (Figure 2) with DNA double strands performed by microscale thermophoresis indicate a sequence dependent recognition. For the tetra-thyminyl derivative 2 a potential for self-association and -aggregation was indicated by mass spectrometry.

Bottom Line: 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.The new tetra-nucleobase binders are synthesized as aza-TANDEM derivatives lacking the N-methylation of triostin A and based on a cyclopeptide backbone.

View Article: PubMed Central - PubMed

Affiliation: Institute of Organic and Biomolecular Chemistry, Georg-August-University Göttingen Tammannstrasse 2, 37077 Göttingen (Germany) E-mail: udieder@gwdg.de.

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.

No MeSH data available.


Related in: MedlinePlus