Design of a new DNA-polyintercalating drug, a bisacridinyl peptidic analogue of Triostin A.
The synthesis of a new bifunctional compound in which two aminoacridine chromophores are linked by the bicyclic depsipeptidic backbone of des-N-tetramethylTriostin A is described. The molecule, bis-[(9-acridinyl)-D-seryl-L-alanyl-L-cysteinyl-L-valine] dilactone disulphide, structurally analogous to the antibiotic anti-tumour drug Triostin A, is shown to possess a high affinity to DNA and to act as a bis-intercalator on the basis of spectroscopic, viscosimetric and thermal-denaturation studies. This model constitutes the first attempt of a synergic association between a peptidic moiety that mimics a naturally occurring drug and aminoacridine, the two parts themselves each exhibiting a high affinity for the DNA target.
D000585:Aminacrine; D055598:Chemical Phenomena; D002621:Chemistry; D004247:DNA; D007364:Intercalating Agents / Q000138:chemical synthesis*; D008956:Models, Chemical; D009842:Oligopeptides / Q000138:chemical synthesis*; D013053:Spectrophotometry
D007364:Intercalating Agents; D009842:Oligopeptides; D000585:Aminacrine; D004247:DNA; C044728:bis((9-acridinyl)seryl-alanyl-cysteinyl-valine)dilactone disulfide