Induced fit conformational changes of a "reversed amidine" heterocycle: optimized interactions in a DNA minor groove complex.

ABSTRACT: To better understand the molecular basis for recognition of the DNA minor groove by heterocyclic cations, a series of "reversed amidine" substituted heterocycles has been prepared. Amidine derivatives for targeting the minor groove have the amidine carbon linked to a central heterocyclic system, whereas in the reverse orientation, an amidine nitrogen provides the link. The reverse system has a larger dihedral angle as well as a modified spatial relationship with the groove relative to amidines. Because of the large dihedral, the reversed amidines should have reduced binding to DNA relative to similar amidines. Such a reduction is observed in footprinting, circular dichroism (CD), biosensor-surface plasmon resonance (SPR), and isothermal titration calorimetric (ITC) experiments with DB613,

SUBMITTER: Munde M 

PROVIDER: S-EPMC2547086 | biostudies-literature | 2007 May

REPOSITORIES: biostudies-literature