BioWorld International Correspondent
Virtual Drug Development Inc. (VDDI) formed a joint venture with two Northern Ireland universities, Queen's University Belfast (QUB) and the University of Ulster, Coleraine, to develop novel peptide-based antibiotics.
The new company, AmphiBiotics Ltd., which will be based in Coleraine and Belfast, is still in start-up mode. "We're trying to secure additional funding from several sources," Brian Walker, professor of biomedicinal chemistry at QUB and one of its scientific founders, told BioWorld International. In addition to seeking venture capital financing, the company also will seek support from U.S. bioterrorism initiatives, including the proposed Project BioShield.
AmphiBiotics combines Walker's research on synthetic peptide synthesis and rational drug design with the work of Chris Shaw at the University of Ulster, who specializes in isolating novel bioactive peptides secreted by amphibians. It also will have access to the REV-4 technology Brentwood, Tenn.-based VDDI recently acquired from Interlink Biotechnologies LLC, of Princeton, N.J. That is designed to improve the stability and tolerability of peptide-based drugs.
The new company's main focus is on multidrug-resistant bacteria, particularly methicillin-resistant Staphylococcus aureus. Shaw's team has isolated a number of peptide leads that can punch holes in bacterial cell membranes.
"Our novel medical peptide drugs kill bacteria by attacking the membrane of the bacteria in a very nonspecific fashion, and because these membranes have evolved over hundreds of millions of years, it is highly unlikely that the microorganisms can mutate quickly enough to develop resistance," he said.
Walker's group has developed an inhibitor to a novel target enzyme, sortase, that is involved in trafficking adherence factors to the bacterial cell surface. "This enzyme is absolutely essential for the initial adherence of bugs to host tissue and cells," Walker said. "This is the first demonstration of inhibition against this enzyme by any group in the world."
His group also is exploring an alternative strategy, based on preventing biofilm formation. Much of the emphasis in that area, Walker said, is on inhibiting the activity of a particular kinase involved in synthesis of alginate, one of the main components of bacterial biofilms. His group has taken an alternative tack, focusing on the inhibition of an upstream peptidase involved in post-translational modification of the kinase.
Walker's group, he said, also will work on developing peptide mimetics with enhanced properties and additional technologies that would optimize drug candidates either for topical administration or systemic use.