Site-directed mutagenesis studies are shedding light on themolecular mechanisms by which interleukin 1 (IL-1) and basicfibroblast growth factor (bFGF) work.
By changing a single amino acid, researchers have convertedhuman IL-1 receptor antagonist (IL-1ra) into a protein thatexhibits some of the growth-stimulating and inflammatoryproperties of IL-1.
In another study, human bFGF lacking six amino acids stillpromoted cell growth, but lost its ability to induce expressionof the clot-busting urokinase plasminogen activator (uPA).
These studies, reported in April's Proceedings of the NationalAcademy of Sciences (PNAS), may lead to more potent drugswith fewer side effects.
Synergen Inc. of Boulder, Colo., is developing IL-1ra to blockthe harmful inflammatory actions of IL-1. When IL-1ra bindsto the IL-1 receptor, IL-1 cannot bind.
Researchers at F. Hoffmann-La Roche Inc. and Synergenreported that substituting a single amino acid in an IL-1raprotein promoted T cell growth and production of theinflammatory agent prostaglandin E2. The mutated IL-1ra wasnot as potent as IL-1, suggesting that more than one amino acidmust be involved in IL-1's interaction with its receptor.
Italian cientists at the University of Brescia and FarmitaliaCarlo Erba S.p.A. in Milan separated bFGF's growth-promotingand uPA-inducing activities. The team reported that bFGFlacking six amino acids bound to bFGF receptors and stimulatedendothelial and fibroblast cell growth. The bFGF analog inducedonly 1 percent as much uPA as bFGF.
Companies developing bFGF include California BiotechnologyInc. of Mountain View and Synergen.
-- Carol Talkington Verser, Ph.D. Special to BioWorld
(c) 1997 American Health Consultants. All rights reserved.