The synthesis of some head to head linked DNA minor groove binders

A series of head to head linked dimers of heterocyclic amino acids has been prepared for investigation of affinity and selectivity in binding to the m inor groove of DNA. The selection of targets for synthesis was led by compu ter based design. Several novel dicarboxylic acid linkers including indoles , phenanthrenes, a fluorenone, and a bisbenzothiophene have been included. Analysis of binding to DNA by footprinting showed high affinity for compoun ds derived from 2,7-dihydrophenanthrene dicarboxylic acid and a predominant selectivity for AT rich regions containing at least 4 AT pairs but with th e ability to span up to two CG base pairs. (C) 2000 Elsevier Science Ltd. A ll rights reserved.