Scientists in the laboratory of associate professor Laszlo Otvos Jr., Ph.D., have spent several years studying an insect-derived antimicrobial peptide called pyrrhocoricin. Both pyrrhocoricin in its native state and lab-created analogs are capable of entering and killing a number of strains of bacteria, including E. coli. Initially interested in pyrrhocoricin and its analogs because of their antimicrobial properties, Otvos and his research team are now exploring whether these peptides could be employed as delivery vehicles for other peptide or peptide-based drugs that would not normally be able to penetrate mammalian cell membranes and tissues.
In their study, published online today in Molecular Pharmaceutics, the researchers showed that native pyrrhocoricin can penetrate human dendritic cells, an important type of immune cell, and that the designer pyrrhocoricin analog can penetrate both dendritic cells and fibroblasts, a cell that produces the collagen fibers that make up connective tissue. The dendritic cells displayed signs of stimulation, which opens the question of whether this peptide delivery system could be used to create new vaccines or immune therapies. The paper will appear in the print edition of the journal in May.
"Our results suggest that our designed pyrrhocoricin analogs are good candidates for transporting peptidic cargo across cell membranes in general, and for potential use in therapeutic applications as well as in vaccine development," Otvos says.
Dendritic cells are a type of antigen-presenting cell, which
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Contact: Marion Wyce
wyce@wistar.upenn.edu
215-898-3943
The Wistar Institute
8-Apr-2004