Robert Sjoholm

Synthesis and DNA-binding Properties of 1,2,3-triazole-linked H-pin Pyrrole- and Imidazole-containing Polyamides Formed by the Huisgen Reaction

Abstract Covalently linked pyrrole (Py)- and imidazole (Im)-containing H-pin polyamides bind in the minor groove of specific DNA sequences with high affinity. The synthesis of 1,2,3-triazole-linked and heterodimeric H-pin polyamides 13a,b formed from the Huisgen reaction of an alkyne-containing f-PyPyPy (6) with an azide-containing f-ImPyIm (7) is reported. The reaction proceeded smoothly under thermal conditions to give an inseparable mixture of 1,4- and 1,5-isomers (13a and 13b, respectively) by column chromatography. When the reaction was conducted under ‘click’ or Cu(I)-catalyzed conditions or in the presence of the cognate DNA sequence, no desired product was observed. Preliminary results from DNA thermal denaturation and circular dichroism titration studies provided evidence of mixture 13a,b binding to the target DNA sequence 5′-TCTCAA-3′.

DNA sequence-selective monoheterocyclic analog of Hoechst 33258: cytotoxicity and antiparasitic properties

Abstract The biophysical and biological evaluations of DNA minor groove binding AT sequence selective benzimidazole analogs of Hoechst 33258 which contain a p-anisyl, a p-[bis(2-chloroethyl)amino]phenyl or a p-anisyl and an amidine moiety are discussed. The preference for all three compounds for the 5′-AAATTT-3′ sequence was ascertained by thermal denaturation and circular dichroism studies. The mustard-containing compound 4 was found to be more cytotoxic against murine cancer cells grown in culture than the non-mustard containing compound. DNA alkylation was not necessary for anti-Leishmanial activity.