“UW Medicine Institute for Protein Design researchers have computationally designed synthetic proteases. Like molecular ‘scissors,’ these enzymes cut another protein at a precise, chosen point.
The researchers specified a target sequence, designed enzymes to cut those targets, and verified their accuracy in doing so across a range of experimental settings. They tested the new enzymes on purified proteins, sequences drawn from proteins implicated in Alzheimer’s disease and amyotrophic lateral sclerosis, and, in one study, inside living human cells cultured in the lab…
Most medicines work by binding: a small molecule or an antibody latches onto its target and holds on, thereby blocking or activating it, one molecule at a time. That one-to-one relationship dictates the medication limit. To engage a million copies of a disease target, one needs a million (or often more) copies of the drug…
Enzymes, however, work on a different scale. An enzyme changes its target and releases its hold, unchanged and ready to act again. A single designed protease can cut thousands to millions of specified targets over its lifetime. This allows it to have the same effect at a substantially lower dose.
The functional properties of proteases also enable therapeutic approaches that would be impossible with a binding agent. These could include destroying a viral protein or a bacterial toxin outright, clearing a misfolded protein that accumulates in neurodegenerative disease, or snipping a protective cap off a drug so it functions only in the tissue where it is needed.”
From UW Medicine Newsroom.
