Discoveries
Strengthening peptides is a 'staple' of fellow's research
Research that involved inserting a minute protein "staple" into a natural compound that activates cell death earned DFCI's Loren Walensky, MD, PhD, an honor at the 2003 meeting of the American Society of Hematology.
Loren Walensky, MD, PhD
Walensky, a postdoctoral fellow in the laboratory of DFCI's Stanley J. Korsmeyer, MD, was one of just eight scientists selected to present their research at the plenary session of the society's gathering in San Diego. His work, uniquely blending chemistry and cell biology, involved restarting the natural cell-death process known as apoptosis, which is often stalled in cancer cells.
A protein called BID contains a short, coiled segment — a helical peptide — that can trigger apoptosis. When the peptide is removed from its parent protein, however, it loses its helical shape. This lessens its biological activity and prevents it from entering cells to deliver its "die" message.
Walensky reasoned that if the peptide were braced from within to keep it from unfolding, it would retain or even enhance its natural potency. Working with Harvard Professor Gregory Verdine, PhD, he constructed a tiny reinforcement, or staple, to do just that. Made from amino acids, the building blocks of proteins, the staple was inserted into the peptide. The stabilized peptide maintained its helical form, was absorbed by laboratory samples of leukemia cells, and activated their cell-death program.
Even more intriguing, when the stapled peptides were injected into mice with human leukemia, the disease's progression was suppressed in preliminary studies. Walensky says the technique may be readily applicable to other signaling proteins involved in cancer and other illnesses.
