Radicicol
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Radicicol, also known as monorden, is a natural product that binds to
Hsp90 Hsp90 (heat shock protein 90) is a chaperone protein that assists other proteins to fold properly, stabilizes proteins against heat stress, and aids in protein degradation. It also stabilizes a number of proteins required for tumor growth, ...
(Heat Shock Protein 90) and alters its function. HSP90 client proteins play important roles in the regulation of the cell cycle, cell growth, cell survival,
apoptosis Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...
,
angiogenesis Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels, formed in the earlier stage of vasculogenesis. Angiogenesis continues the growth of the vasculature by processes of sprouting and splitting ...
and
oncogenesis Carcinogenesis, also called oncogenesis or tumorigenesis, is the formation of a cancer, whereby normal cells are transformed into cancer cells. The process is characterized by changes at the cellular, genetic, and epigenetic levels and abnor ...
.


Biosynthesis

Biosynthesis of Radicicol has been best studied in '' Pochonia chlamydosporia'', in which the majority of the core structure is produced in vivo through iterative type I
polyketide synthases Polyketides are a class of natural products derived from a precursor molecule consisting of a chain of alternating ketone (or reduced forms of a ketone) and methylene groups: (-CO-CH2-). First studied in the early 20th century, discovery, biosynth ...
. This structure produced is the earliest intermediate in the radicicol biosynthesis, monocillin II. This intermediate is transformed to radicicol through halogenation and epoxide formation performed by RadH and RadP respectively. These enzymes are coded by the genes Rdc2 and Rdc4 in the pathway, and removing either of these results in a product that has the monocillin II core, but does not have either the epoxide or halogen added.


See also

*
Geldanamycin Geldanamycin is a 1,4-benzoquinone ansamycin antitumor antibiotic that inhibits the function of Hsp90 (Heat Shock Protein 90) by binding to the unusual ADP/ATP-binding pocket of the protein. HSP90 client proteins play important roles in the regulat ...


References


Further reading

*{{cite journal , vauthors=Winssinger N, Barluanga S , title=Chemistry and biology of resorcylic acid lactones , journal=Chem Commun , volume= 13, issue=1 , pages=22–36 , date=January 2007 , doi=10.1039/B610344H , pmid=17279252 Review of the chemistry and biology of resorcylic acid lactones, including radicicol. Epoxides Macrolides Halogen-containing natural products Polyketides Chloroarenes