EFFECTS OF NEUTRALIZATION PATTERN AND STEREOCHEMISTRY ON DNA BENDING BY METHYLPHOSPHONATE SUBSTITUTIONS

Asymmetric phosphate neutralization has been hypothesized to play a ro le in DNA bending by proteins, Neutralization is thought to involve sa lt bridges between the negatively charged phosphate backbone of duplex DNA and the cationic amino acids of an approaching protein, According to this model, the resulting unbalanced charge distribution along the duplex DNA induces the double helix to collapse toward the neutralize d surface, Previous work has confirmed that DNA bending is induced by the asymmetric incorporation of racemic methylphosphonate linkages cre ating a neutral region on one face of duplex DNA, Neutralization was a ccomplished by substitution of three consecutive phosphodiesters on ea ch strand, arranged across one minor groove of the DNA (a total of six neutralized phosphates), We now measure DNA bending induced by a more diffuse patch of neutralization (alternating neutralized and anionic phosphates) and explore the effect of methylphosphonate stereochemistr y. DNA duplexes with patches of alternating methylphosphonate and phos phodiester linkages are less bent than DNAs wherein consecutive phosph ates are neutralized Furthermore, duplexes neutralized by incorporatio n of pure (RP)methylphosphonate isomers are bent similar to 30% less t han duplexes neutralized by racemic methylphosphonates.