Students Design, Synthesize And Test New Reagents As Part of UB Pharmacy Course

Release Date: May 2, 1995 This content is archived.

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BUFFALO, N.Y. -- Spring is when most college students are writing papers or studying for exams. But in an innovative, senior-level class in the University at Buffalo School of Pharmacy, students have been given a unique assignment: Design, synthesize and test a new pharmacological reagent that could lead to more effective cardiovascular treatments.

During the semester-long assignment, the students enrolled in "Molecular Biology and Immunology Methods in Pharmacology" learned about the trials and tribulations of drug development and then were challenged to put their new knowledge to the ultimate test.

"This is not the typical 'cookbook-type' lab that most undergraduate laboratories are," said Linda Hall, Ph.D., professor of biochemical pharmacology who teaches the course with colleague Stanley Halvorsen, Ph.D., assistant professor. "Instead, we asked students to design a new pharmacological reagent based on molecular biology principals."

To earn credit for the class, students had to design, synthesize and test ribozymes, a new type of pharmacological reagent considered one of the most exciting approaches in disease treatment today.

Hall said the UB students' work is the first known attempt anywhere to use ribozymes in tests that could eventually have application to new cardiovascular treatments.

Ribozymes are pieces of genetic material called ribonucleic acid (RNA) that can be designed to recognize and attack specific sequences of RNA involved in the production of disease molecules. In this class, the students designed ribozymes to attack RNA that makes a specific calcium channel.

Hall explained that some of the symptoms of cardiovascular disease can be modulated by blocking calcium channels or reducing their activity.

"I tell my students ribozymes are like genetic police with guns," said Hall. "They are very efficient killers of problem molecules."

To do the work, the class was divided into five groups of two students. Each pair synthesized a different ribozyme, but all of the reagents were designed with the objective of inhibiting the synthesis of a specific calcium channel.

Calcium channels are found in cells that process information; they play a key role in skeletal muscle and heart function and are targets for numerous cardiovascular drugs.

"Cardiovascular drugs that are calcium-channel blockers work well, but because all calcium channels have similar architectures, they can have side effects on other calcium channels that are not targeted," explained Hall.

And because they work from inside the cell, ribozymes do not diffuse throughout the body, offering the potential for more precise pharmacological action and fewer side effects.

Using computerized drug-design methods similar to those used in the pharmaceutical industry and computer programs supported by UB's Center for Advanced Molecular Biology and Immunology, the students designed new ribozymes targeted against specific calcium-channel sites they identified. They chemically synthesized the new reagents in the laboratory and injected them into frogs' eggs, a common model for testing gene actions.

Last week, they tested the action of their ribozymes and five out of five were shown to have inhibited the synthesis of the targeted calcium channel.

"These results are preliminary, but they are very exciting," said Hall, adding that researchers in her lab will be conducting additional tests with the new reagents.

The advanced equipment the students worked on was provided by a National Science Foundation grant, with matching funds from the dean of the UB School of Pharmacy, the UB Provost's Office and industrial sponsors. Hall said additional funding is needed to purchase chemicals, frogs' eggs and other supplies for future classes.

Media Contact Information

Ellen Goldbaum
News Content Manager
Medicine
Tel: 716-645-4605
goldbaum@buffalo.edu