Researchers at the University of Pennsylvania School of Medicine have designed peptides that are able to bind to specific regions of transmembrane proteins, using computer algorithms, and information from existing protein sequence and structure databases.
"We can now actually interrogate parts of proteins within the membrane," says William F. DeGrado, Ph.D., professor of biochemistry and biophysics. "We used computer programs to design peptides that can bind to only one of a number of closely related membrane proteins."
The research looked at how the binding of these designed peptides affected the crucial first steps in blood clotting. The researchers targeted two transmembrane proteins called integrins that influence the behavior of platelets. When the designed peptide is inserted into the platelet membrane it binds to the portion of the integrin within the membrane and subsequently perturbs another function in the clotting process downstream.
The researchers examined two integrins, áIIbâ3 and áVâ3. In the study, they found that the áIIbâ3 integrin, the most prominent integrin on platelets, is involved in making platelet aggregates. The other integrin behaves much like áIIbâ3, in that it causes platelets to stick to certain proteins on the outside of the cell.
The study appeared in the March 30 issue of Science.