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Synthesis of Cyclopeptidic Analogues of Triostin A with Quinoxalines or Nucleobases as Chromophores
Author(s) -
Dietrich Björn,
Diederichsen Ulf
Publication year - 2005
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200400548
Subject(s) - chemistry , nucleobase , intercalation (chemistry) , chromophore , stereochemistry , bicyclic molecule , covalent bond , dna , combinatorial chemistry , hydrogen bond , peptide , cyclic peptide , peptidomimetic , organic chemistry , molecule , biochemistry
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)