CRYSTAL STRUCTURES OF TWO FURAN DERIVATIVES OF BERENIL AND d(CGCGAATTCGCG)₂. John O. Trent, Stephen Neidle, George R. Clark⁺, and David W. Boykin⁺⁺. The CRC Biomolecular Structure Unit, The Institute of Cancer Research, Sutton, Surrey, SM2 5NG, U.K.; ⁺Chemistry Department, University of Auckland, New Zealand; ⁺⁺Department of Chemistry and Biotechnology and Drug Design, Georgia State University, U.S.A.

DNA minor groove binding bis-benzamidine derivatives such as berenil, propamidine, and pentamidine have been shown to bind to AT-rich base-pair regions. Two furan derivatives of berenil with alkyl substitued benzamidines complexed with d(CGCGAATTCGCG)₂ have been determined to 2.2 Å resolution and refined to R factors of 16.9 and 18.6%.

The cyclopropane and isopropyl substituents are orientated away from the floor of the minor groove with no penalty to binding. The drugs are located in the minor groove by two strong amidine hydrogen bonds to the O₂ of the thymines situated at the ends of the AT-rich region. The isopropyl substituted derivative has a tight hydrogen bonded water network in the minor groove at one amidine site which changes the orientation of the isopropyl substituent. The overall effect of this alkyl benzamidine substitution is to increase the binding of the drugs to the minor groove.