BOSTON – May 19, 2008 – Being able to target the genetic code to develop an effec­tive treat­ment of a dis­ease is the ulti­mate goal for many sci­en­tists. Focusing on how the DNA inter­acts with a poten­tial drug is an impor­tant ele­ment of DNA therapy research. Mark Williams, Ph.D., Asso­ciate Pro­fessor of Physics at North­eastern University’s Col­lege of Art­sand Sci­ences, and his research team have devel­oped a method using optical tweezers to better under­stand how those inter­ac­tions occur.

This research, per­formed pri­marily by grad­uate stu­dent Thaya Para­manathan, pub­lished in a recent edi­tion of the Journal of the Amer­ican Chem­ical Society (vol. 130, p. 3752), has the poten­tial to uncover cru­cial infor­ma­tion about how to target DNA in order to develop ther­a­pies for chronic dis­eases such as cancer and AIDS.

DNA, the struc­ture that holds the human genetic code, is com­posed of nucleic acid bases pairing up and bonding together to form a double helix. Inter­ca­la­tors are mol­e­cules that bind between DNA base pairs and have been found to inhibit cell repli­ca­tion, a highly desired quality for poten­tial drug tar­gets. Novel “threading” inter­ca­la­tors have recently been devel­oped to opti­mize DNA binding. Due to the strength of these bonds and the slow rate of binding, how­ever, it is hard to study the inter­ac­tions of these inter­ca­la­tors using normal methods, resulting in a lim­ited avail­ability of data and research options.

To address these issues, Mark Williams and his team stretched single DNA mol­e­cules using optical tweezers to better con­trol the inter­ac­tions between the DNA and the poten­tial drug target molecules.

By studying this threading mech­a­nism on a single DNA mol­e­cule, we were able to directly mea­sure the phys­ical char­ac­ter­is­tics of the inter­ac­tions between the DNA and poten­tial DNA binding drugs,” said Williams.

The optical tweezers grab the ends of the DNA strand and stretch it out, allowing for the DNA strands to sep­a­rate more quickly. When the DNA bases sep­a­rate, the drug mol­e­cule, which is dumbbell-​​shaped and binds with the DNA in the center of the dumb-​​bell, slides in between the base pairs. When the bond re-​​forms between the base pairs, the poten­tial drug mol­e­cule remains stuck between the DNA strands that form the double helix, and there­fore­forms a very strong bond.

The obser­va­tions lead to the under­standing of how and under what cir­cum­stances these bonds occur, which can help in the devel­op­ment of drug ther­a­pies that would inhibit or pre­vent mutated cells from replicating.

The ability to pre­cisely quan­tify and char­ac­terize the phys­ical mech­a­nism of this threading inter­ca­la­tion should help to fine-​​tune the desired DNA binding prop­er­ties,” added Williams.

For more infor­ma­tion about this research paper, please con­tact Jenny Eriksen at (617) 373‑2802 or via email at j.​eriksen@​neu.​edu. For addi­tional infor­ma­tion about Pro­fessor Williams’ research, click on the fol­lowing link: http://​nuweb​.neu​.edu/​m​a​rk/

About North­eastern

Founded in 1898, North­eastern Uni­ver­sity is a pri­vate research uni­ver­sity located in the heart of Boston. North­eastern is a leader in inter­dis­ci­pli­nary research, urban engage­ment, and the inte­gra­tion of class­room learning with real-​​world expe­ri­ence. The university’s dis­tinc­tive coop­er­a­tive edu­ca­tion pro­gram, where stu­dents alter­nate semes­ters of full-​​time study with semes­ters of paid work in fields rel­e­vant to their pro­fes­sional inter­ests and major, is one of the largest and most inno­v­a­tive in the world. The Uni­ver­sity offers a com­pre­hen­sive range of under­grad­uate and grad­uate pro­grams leading to degrees through the doc­torate in six under­grad­uate col­leges, eight grad­uate schools, and two part-​​time divi­sions. For more infor­ma­tion, please visit www​.north​eastern​.edu.