Synthesis of beta-carboline derivatives and their interaction with duplex-DNA

3-Amino-9-N-(2-aminoethyl)carbamoylethyl-beta-carboline (3) was synthesized from 3-methoxycarbonyl-beta-carboline through successive cyanoethylation, Curtius rearrangement, and addition reaction of ethylenediamine in 45 % ove rall yield. The terminal aliphatic amino group of 3 was transformed to a N- methylureido group with succinimidyl N-methylcarbamate to afford a compound 4 in 80% yield. Affinity of 3, 4, P-carboline (1), and 3-amino-beta-carbol ine (2) to a DNA oligomer or calf thymus DNA was spectrophotometrically stu died. Optical spectroscopy of these beta-carbolines showed 25 similar to 65 nm bathochromic shifts of the light absorption bands upon binding to the n ucleic acids, which suggests binding by intercalation. Scatchard plots, obt ained by fluorescence titration, gave the corresponding binding constants K -D to the DNA oligomer; 7.45 x 10(3), 5.13 x 10(5), 7.34 x 10(5), and 7.01 x 10(5), respectively. The terminal aliphatic amino group considerably decr eases the intercalating ability of 3 to DNA.