The common dogfish shark has become the latest source fornovel compounds that may act as powerful antibiotics inhumans.
Researchers from Magainin Pharmaceuticals Inc. and theChildren's Hospital of Philadelphia reported in this week's issueof Proceedings of the National Academy of Sciences (Vol. 90,Feb. 1993) the isolation and characterization of a uniquesteroid-like substance, squalamine, from the stomach and otherorgans of the shark Squalus acanthias.
University of Pennsylvania School of Medicine researchersKaren Moore, Michael Zasloff (currently the vice president ofMagainin) and their associates reported that the water-solublecationic steroid they isolated from stomach extracts exhibitspotent anti-microbial activity against fungi, protozoa and bothgram-negative and gram-positive bacteria.
Because they also found squalamine in the shark's liver andgallbladder, as well as in other organs in lesser amounts, thescientists speculated that squalamine may serve as a systemicanti-microbial agent in this animal, although its biosyntheticpathway and role in host self-defense are still awaitinginvestigation.
Magainin has licensed the exclusive worldwide rights tosqualamine from the Children's Hospital, to which any patentrights will be assigned. The relationship between the PlymouthMeeting, Pa., company and the hospital stems from the dayswhen Magainin sponsored then University of Pennsylvaniaresearcher Zasloff's work, explained Jay Moorin, president andchief executive officer of Magainin (NASDAQ:MAGN).
In fact, it was Zasloff who discovered that certain frogs produceyet another novel antibiotic compound, a magainin, or host-defense peptide. "By applying what he learned with magainin,Zasloff identified squalamine in sharks," Moorin told BioWorld."We've also identified compounds from two other animals,"Moorin added, "but we haven't characterized them yet."
A relative of that first magainin is currently in Phase II clinicaltrials as a broad-spectrum topical antibiotic. But it's a far cryfrom the original compound Zasloff isolated from frogs. "Thefirst magainin was a 23-amino acid peptide. Using chemicalmethods, we modeled 2,000 different analogs," Moorin said."The compound that is in Phase IIs -- which we madesynthetically in our labs -- is 100 times more efficacious thanthe first magainin."
This may prove to be the case for squalamine, as well. Thescientists have gone on to chemically synthesize squalamineand have demonstrated that the "synthetic compound isidentical to the natural substance in its physical and biologicalproperties." But Magainin researchers still need to "do thestructure-activity work in the lab," Moorin said. "We could endup with another molecule" or it could show activity in itsoriginal form.
-- Jennifer Van Brunt Senior Editor
(c) 1997 American Health Consultants. All rights reserved.