Magainin

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Magainin
Identifiers
SymbolMagainin
TCDB1.C.16
OPM superfamily211
OPM protein2mag

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] They were named by Zasloff, after the Hebrew word for "shield," מגן māgēn (Ashkenazi pronunciation: magain).[3]

Zasloff helped found a company, Magainin Pharmaceuticals (subsequently called Genaera) to develop magainins into drugs.[4] 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][5][6] Another company, Dipexium Pharmaceuticals, ran further phase III clinical trials for the same use, which failed in 2016.[7]

References[edit]

  1. ^ Magainins at the US National Library of Medicine Medical Subject Headings (MeSH)
  2. ^ a b c Conlon JM, Mechkarska M, King JD (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.
  3. ^ Interviewed in 1987, Zasloff explained: "I used it because it came from the skin and it was shielding, in my opinion. What the hell, I hadn't heard a Hebrew name in science before" (Susan Okie (July 30, 1987). "Frog's Skin Yields Powerful Antibiotic". The Washington Post.). In a later interview, his wife, Barbara Zasloff, added: "Tradition would have it that he would have given it a Latin or Greek name. We both felt that he comes from a Hebrew tradition and it would be very appropriate to give it a Hebrew name" (Susan Okie (February 16, 1988). "A Man and His Frogs". The Washington Post.).
  4. ^ George J (April 29, 2009). "Biotech Genaera shutting down: Never brought drug to market". Philadelphia Business Journal.
  5. ^ 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.
  6. ^ "Pexiganan". AdisInsight. Retrieved 16 January 2018.
  7. ^ "Dipexium's Diabetic Foot Ulcer Candidate Fails Phase III Trials". GEN. October 25, 2016.