No abstract

The interaction of AMSA with nucleic acids was studied by several techniques. Melting temperature and CD studies equally suggest that AMSA-binding is interfering with the secondary structure of DNA. An overlap by two mechanism of binding seems to exist. Based on the CD measurements at low drug concentration intercalation is the most likely way of binding. At higher drug concentration stacking interaction predominates leading to cooperativity and formation of oriented sheets of aromatic ring-systems as reflected in the optical activity induced in the metachromatic band of the achiral drug. No base-pair specificity could be confirmed; however, a high affinity of AMSA to poly(A) chains was demonstrated. The CD measurements did not indicate any significant interaction with RNA. The selectivity of the AMSA-DNA interaction can be regarded as an important argument in favour of the role of this interaction in the anti-tumour effect of the drug.

Branched polypeptides were synthesized with the general formula poly(Lys-(Xi)) or poly(Lys-(DL-Alam-Xi)), where X = Leu or D-Leu, i < 1, 1 < m < 2. Coupling of Leu or D-Leu to poly(Lys) was achieved by the active ester method. The short DL-Ala oligomers were joined to the side chains by polymerisation of N-carboxy-DL-Ala anhydride. The CD measurements performed in water solutions of various pH and ionic strength indicated that joining Leu or D-Leu directly to Lys ε-amino groups increases dramatically the helix forming tendency. However, this ability was somewhat less pronounced with the D-enantiomer of Leu in accordance with our previous observations concerning the role of configuration. The polypeptide with short DL-Ala oligomers as outside determinants was investigated extensively even in trifluoroethanol-water mixtures and SDS solutions. No significant conformational influence could be demonstrated by the elongation of the branches with 1-2 DL-Ala residues.