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]

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

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]

ReferencesEdit

  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.