Selective DNA-Binding by Designed Bisbenzamidine-Homeodomain Chimeras

Abstract

We report the construction of conjugates between three variants of the helix 3 region of a Q50K engrailed homeodomain and bisbenzamidine minor-groove DNA binders. The hybrid featuring the sequence of the native protein failed to bind to DNA; however, modifications that increased the α-helical folding propensity of the peptide allowed specific DNA binding by a bipartite (major/minor groove) interactionMinisterio de Economía y Competitividad. Grant Numbers: SAF2010-20822-C02, CTQ2012-31341 Consolider Ingenio. Grant Number: 2010 CSD2007-00006 Xunta de Galicia. Grant Number: GRC2013/14 European Regional Development Fund European Research Council. Grant Number: Na 340055 Ministerio de Ciencia e Innovación Fundación Gil DávilaS