An international team of researchers has designed and conducted initial tests on molecules that have the potential to treat diseases involving inflammation, such as asthma, rheumatoid arthritis, stroke and sepsis.
The team started by creating a three-dimensional map of a protein structure called the C3a receptor, which sits on the surface of human cells and plays a critical role in regulating a branch of the immune system called the complement system. They then used computational techniques to design short portions of protein molecules, known as peptides, that they predicted would interact with the receptor and either block or enhance aspects of its activity. Finally, experimentalists validated the theoretical predictions by synthesizing the peptides and testing them in animal and human cells.
The researchers – a collaboration of teams at four institutions on three continents – published their results May 10 in the Journal of Medicinal Chemistry.
The collaboration includes Christodoulos Floudas, the Stephen C. Macaleer ’63 Professor of Engineering and Applied Science in the Department of Chemical and Biological Engineering at Princeton University; Dimitrios Morikis, professor of bioengineering at the University of California, Riverside; Peter Monk of the Department of Infection and Immunity at the University of Sheffield Medical School, U.K.; and Trent Woodruff of the School of Biomedical Sciences at the University of Queensland, Australia.