Synthesis of Cyclopeptidic Analogues of Triostin A with Quinoxalines or Nucleobases as Chromophores

• Published in: European journal of organic chemistry Vol. 2005; no. 1; pp. 147 - 153
• Main Authors: Dietrich, Björn, Diederichsen, Ulf
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01.01.2005; WILEY‐VCH Verlag; Wiley
• Subjects: Amino acids; Bis(intercalator); Chemistry; Chemistry, Organic; Cyclic peptides; Nucleic acids; Physical Sciences; Science & Technology; Triostin A; DNA-BINDING; ANTIBIOTICS; MOLECULAR-STRUCTURE; bis(intercalator); amino acids; INTERCALATION CHROMOPHORE; triostin A; nucleic acids; SOLUTION-PHASE SYNTHESIS; cyclic peptides; KEY SANDRAMYCIN ANALOGS; SEQUENCE SPECIFICITY; DES-N-TETRAMETHYLTRIOSTIN; PEPTIDE-SYNTHESIS; SYSTEMATIC EXAMINATION
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.200400548

The natural antibiotic triostin A (1) is based on a conformationally rigid disulfide‐bridged cyclo‐octadepsipeptide scaffold. This bicyclic core structure provides a perfect preorganization of two covalently attached quinoxalines resulting in sequence‐specific bis(intercalation) of the chromophores in double‐stranded DNA. Herein for the first time the corresponding cyclopeptide has been synthesized as a scaffold instead of the cyclodepsipeptide of triostin A by solid‐phase peptide synthesis followed by bis(cyclization) in solution. Furthermore, when in contact with DNA the bicyclic peptide provides additional hydrogen‐bonding possibilities and greater conformational rigidity in comparison to triostin A. These modifications to the backbone of triostin A might be especially valuable in combination with the use of nucleobases instead of quinoxalines for additional DNA recognition next to bis(intercalation) like major groove binding or detection of abasic DNA damages. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)