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{{Short description|Group of pore-formng peptides from the skin and intestines of frogs}} |
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{{multiple issues| |
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{{cs1 config|name-list-style=vanc}} |
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{{POV|date=October 2016}} |
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{{this|antimicrobial peptides|the alloy|Manganin}} |
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{{refimprove|date=October 2016}} |
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{{Infobox protein family |
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{{update|date=October 2016}} |
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| Symbol = Magainin |
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| Name = Magainin |
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| image = |
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| width = |
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| caption = |
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| Pfam = |
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| Pfam_clan = |
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| InterPro = |
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| SMART = |
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| PROSITE = |
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| MEROPS = |
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| SCOP = |
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| TCDB = 1.C.16 |
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| OPM family = 211 |
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| OPM protein = 2mag |
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| CAZy = |
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| CDD = |
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}} |
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The '''magainins''' are a class of [[antimicrobial peptides]] found in the [[African clawed frog]] (''Xenopus laevis'').<ref>{{MeshName|Magainins}}</ref> |
The '''magainins''' are a class of [[antimicrobial peptides]] found in the [[African clawed frog]] (''Xenopus laevis'').<ref>{{MeshName|Magainins}}</ref> 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.<ref name=Conlon/> |
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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.<ref name=Conlon>{{cite journal | vauthors = Conlon JM, Mechkarska M, King JD | title = Host-defense peptides in skin secretions of African clawed frogs (Xenopodinae, Pipidae) | journal = General and Comparative Endocrinology | volume = 176 | issue = 3 | pages = 513–8 | date = May 2012 | pmid = 22036891 | doi = 10.1016/j.ygcen.2011.10.010 }}</ref> They were named by Zasloff, after the [[Hebrew]] word for "shield," מגן māgēn ([[Ashkenazi Hebrew|Ashkenazi]] pronunciation: magain).<ref>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" ({{cite news|author=Susan Okie|title=Frog's Skin Yields Powerful Antibiotic|url=https://www.washingtonpost.com/archive/politics/1987/07/30/frogs-skin-yields-powerful-antibiotic/f4b40db2-4780-46d0-b93d-211d8178767e|newspaper=The Washington Post|date=July 30, 1987}}). 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" ({{cite news|author=Susan Okie|title=A Man and His Frogs|url=https://www.washingtonpost.com/archive/lifestyle/wellness/1988/02/16/a-man-and-his-frogs/8ae0f57d-5c40-4c52-be7f-47105159d5cb|newspaper=The Washington Post|date=February 16, 1988}}).</ref> |
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==Discovery== |
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Zasloff was using the [[oocytes]] of ''[[Xenopus]]'' to study the nuclear transport and processing of tRNA. After removal of the ovaries of these frogs, He would suture the abdominal wounds and return the frogs to the aquarium he maintained in his laboratory. One day, many years into this research, he was struck by the remarkable manner in which these frogs healed. Wounds closed in the non-sterile tanks without any evidence of infection or visible inflammation. This "eureka" moment, his appreciating this "mysterious" process of healing, suggested to him that some mechanism had to exist by which these frogs fought off the microbes within the tank. He [[hypothesized]] that some form of antimicrobial agent was being expressed on the skin. Within several months these agents were isolated, chemically identified as [[peptides]], and [[Chemical synthesis|synthesized]] in the laboratory. |
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Zasloff helped found a company, Magainin Pharmaceuticals (subsequently called Genaera) to develop magainins into drugs.<ref>{{cite news|last1=George|first1=John |title=Biotech Genaera shutting down: Never brought drug to market |url=https://www.bizjournals.com/philadelphia/stories/2009/04/27/daily31.html |work=Philadelphia Business Journal |date=April 29, 2009}}</ref> One candidate was an analog of magainin called pexiganan (MSI-78) that the company developed as a topical agent for infected [[diabetic foot ulcer]]s; in 1999 the FDA rejected the application because pexiganan was not better than standard treatments.<ref name=Conlon/><ref>{{cite journal | vauthors = Moore A | title = The big and small of drug discovery. Biotech versus pharma: advantages and drawbacks in drug development | journal = EMBO Reports | volume = 4 | issue = 2 | pages = 114–7 | date = February 2003 | pmid = 12612596 | pmc = 1315844 | doi = 10.1038/sj.embor.embor748 }}</ref><ref>{{cite web|title=Pexiganan|url=http://adisinsight.springer.com/drugs/800002904|publisher=AdisInsight|access-date=16 January 2018|language=en}}</ref> Another company, Dipexium Pharmaceuticals, ran further phase III clinical trials for the same use, which failed in 2016.<ref>{{cite news|title=Dipexium's Diabetic Foot Ulcer Candidate Fails Phase III Trials|url=https://www.genengnews.com/gen-news-highlights/dipexiums-diabetic-foot-ulcer-candidate-fails-phase-iii-trials/81253359|work=GEN|date=October 25, 2016}}</ref> |
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Their discovery represented the first example of an antimicrobial peptide produced in the skin of an animal, and complemented prior studies by Hans Boman of Sweden in the [[Hyalophora cecropia|Cecropia moth]], and Robert Lehrer (US) in rabbit [[white blood cells]] ([[defensins]]), supporting the widespread existence of antimicrobial peptides throughout nature. Thousands of antimicrobial peptides, similar to magainin, have been found throughout the plant and animal kingdoms. Many exhibit broad-spectrum antimicrobial activity, and can inhibit growth of numerous species of bacteria and fungi, as well as induce [[osmotic lysis]] of [[protozoa]]. These antimicrobial peptides are components of the "[[innate immune system]]" of animals and provide an important first line of antimicrobial defense. |
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An excellent review of antimicrobial peptides, covering their diversity and mechanism of action, has been published.<ref>{{cite journal | last1 = Zasloff | first1 = Michael | title = Antimicrobial peptides of multicellular organisms | journal = [[Nature (journal)|Nature]] | volume = 415 | issue = 6870 | pages = 389–395 | year = 2002 | doi = 10.1038/415389a | pmid=11807545}}</ref> |
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| ⚫ | |||
{{reflist}} |
{{reflist}} |
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{{Membrane proteins}} |
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{{Pore-forming toxins}} |
{{Pore-forming toxins}} |
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[[Category:Antimicrobial peptides]] |
[[Category:Antimicrobial peptides]] |
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{{biochem-stub}} |
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Latest revision as of 20:37, 26 October 2024
| Magainin | |
|---|---|
| Identifiers | |
| Symbol | Magainin |
| TCDB | 1.C.16 |
| OPM superfamily | 211 |
| OPM protein | 2mag |
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]- ^ Magainins at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- ^ 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.
- ^ 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.).
- ^ George J (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.