This technology should help solve the puzzles of
cancer, Alzheimer’s, atherosclerosis and infectious diseases.
Santa Barbara, California – May 1 , 2006 – Researchers at UC Santa
Barbara have developed a new biotechnology that enables scientists to
identify and engineer protease substrates, giving them the means of
crafting pharmaceuticals to outsmart disease. Their work, authored by
Patrick Daugherty, an assistant professor of Chemical Engineering, and
Kevin Boulware, a PhD candidate, are published online today in the
Proceedings of the National Academy of Sciences.
Proteases (or peptidases) are encoded by about two percent of genes in
the human genome and play key roles in nearly all diseases. They act as
"molecular scissors" by attaching to specific sequences contained within
other proteins, called substrates, and cutting them in specific
locations. For example, proteases are responsible for digesting food,
for determining the proper time for cells to die, and for removing
damaged proteins from the body.
But the substrates for most proteases are unknown, and this has limited
researchers’ ability to facilitate or thwart protease action. By
identifying substrates, scientists gain the ability to regulate protein
function, creating the capacity to speed up, slow down or eliminate
particular protease actions. Daugherty’s approach also makes it easier
to measure protease action and thus develop pharmaceuticals that control
Daugherty and Boulware developed a general combinatorial approach to
identify optimal substrates of proteases, using quantitative kinetic
screening of cellular libraries of peptide substrates (CLiPS). The
results suggest that CLiPS will be broadly useful for characterizing
proteases and developing optimal substrates for therapeutic
Of the roughly 1,000 proteases in the human genome, only about ten
percent of the targets have been identified, but Daugherty believes that
scientists will identify nearly all of them in the next five to ten
years. "This technology will give us a scalable tool that will allow us
to effectively tackle this challenge," he says.