NOVEL CLASS OF DNA BINDING MOTIFS BASED ON BISTETRAHYDROFURAN AND BISFURAN SKELETON WITH LONG ALKYL CHAINS

Abstract

Small molecules with DNA-binding affinity within the minor groove have become of great interest. In this paper, new DNA binding molecules; diamino-bistetrahydrofuran (bisTHF) and diamino-bisfuran are reported. The bisTHF ligand with RR configuration at the amino groups and C8 alkyl chains (RR8) stabilized GC-rich duplex. In contrast, bisfuran compounds stabilized AT-rich duplex. The binding affinity of RR8 with 12 mer duplex DNA was determined by isothermal titration calorimetry to be 3.3 × 10⁸ M⁻¹.

ACKNOWLEDGMENTS

This work was supported by Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture, Japan (C09672146 to SS). We also grateful to Professor Tomofumi Miyamoto, Graduate School of Pharmaceutical Sciences, Kyushu University, Japan, for X-ray analysis of the meso phthalimide derivative of 10.