Magainin
The magainins are a class of antimicrobial peptides found in the African clawed frog (Xenopus laevis).[1] The peptides are cationic, generally lack a stable conformation in water but form amphipathic α-helix in membranes; their mechanism against micro-organisms is unclear but they disrupt the cell membranes of a broad spectrum of bacteria, protozoa, and fungi.[2]
They were independently discovered at around the same time by the labs of Michael Zasloff at the NIH and Dudley H. Williams at the University of Cambridge.[2]
Zasloff helped found a company, Magainin Pharmaceuticals (subsequently called Genaera) to develop magainins into drugs.[3] One candidate was an analog of magainin called pexiganan (MSI-78) that the company developed as a topical agent for infected diabetic foot ulcers; in 1999 the FDA rejected the application because pexiganan was not better than standard treatments.[2][4][5] Another company, Dipexium Pharmaceuticals, ran further phase III clinical trials for the same use, which failed in 2016.[6]
References
- ^ Magainins at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- ^ a b c Conlon, JM; Mechkarska, M; King, JD (1 May 2012). "Host-defense peptides in skin secretions of African clawed frogs (Xenopodinae, Pipidae)". General and comparative endocrinology. 176 (3): 513–8. doi:10.1016/j.ygcen.2011.10.010. PMID 22036891.
- ^ George, John (April 29, 2009). "Biotech Genaera shutting down: Never brought drug to market". Philadelphia Business Journal.
- ^ Moore, A (February 2003). "The big and small of drug discovery. Biotech versus pharma: advantages and drawbacks in drug development". EMBO reports. 4 (2): 114–7. doi:10.1038/sj.embor.embor748. PMC 1315844. PMID 12612596.
- ^ "Pexiganan". AdisInsight. Retrieved 16 January 2018.
- ^ "Dipexium's Diabetic Foot Ulcer Candidate Fails Phase III Trials". GEN. October 25, 2016.