In Vitro Binding of Platinum Anticancer Drugs to DNA Observed Directly by Polyacrylamide Gel Electrophoresis: A Multiweek Undergraduate Laboratory Investigation

Structure-activity relationships are foundationalconceptsin biochemistry and drug design. Despite their importance, it canbe difficult to create and execute laboratory activities that allowstudents to directly observe the interactions between small-moleculedrugs and their biomolecular targets. Here, we report an activitythat investigates the binding of well-known platinum drugs to short,double-stranded DNA hairpin structures. Students chose multiple Ptdrugs to investigate, along with one or more different experimentalconditions, performed the Pt-DNA binding reactions, and thencharacterized the samples by denaturing polyacrylamide gel electrophoresis.Then, they rationalized their gel data on the basis of the structuresof the Pt drugs and of double-stranded DNA. In addition to experimentallyobserving Pt-DNA interactions, students used molecular visualizationsoftware to identify other drug interactions with nucleic acids usingstructures obtained from the Protein Data Bank to determine theirmode of binding. The activity was performed by upper-level undergraduatebiochemistry students over 3 weeks and uses inexpensive equipmentcommonly found in any standard undergraduate biochemistry teachinglaboratory. It affords an excellent opportunity for students to manipulateand characterize macromolecular structures and directly connect theseexperimental observations to important concepts in drug chemistry,bioinorganic chemistry, and chemical biology.

Automated summary

This study presents an experimental activity that allows students to observe the interaction between small-molecule drugs and biomolecular targets by investigating the binding of platinum drugs to DNA structures. Students choose platinum drugs, perform Pt-DNA binding reactions, characterize the samples, and rationalize the results based on drug and DNA structures. Additionally, students use molecular visualization software and structures from the Protein Data Bank to identify other drug-nucleic acid interactions. This activity provides a valuable opportunity for students to manipulate macromolecular structures and connect their experimental observations to important concepts in drug chemistry and chemical biology.