Covalent Reactions of Wortmannin under Physiological Conditions Academic Article uri icon


MeSH Major

  • Androstadienes


  • Wortmannin (Wm), a steroid-like molecule of 428.4 Da, appears to be unstable in biological fluids (apparent chemical instability), yet it exhibits an antiproliferative activity in assays employing a 48 hr incubation period (prolonged bioactivity), a situation we refer to as the "wortmannin paradox." Under physiological conditions, Wm covalently reacts with nucleophiles such as the side chains of cysteine, N-methyl hexanoic acid, lysine, or proline at the C20 position on the furan ring. Like Wm, WmC20 amino acid derivatives had significant antiproliferative activities. Three Wm derivatives, WmC20-proline, WmC20-cysteine, and a WmC20-N-methyl hexanoic acid, generated Wm that then reacted with lysine in an exchange-type reaction. This unusual, reversible, covalent reaction of Wm with nucleophiles under physiological conditions provides an explanation for the wortmannin paradox.

publication date

  • March 2007



  • Academic Article



  • eng

Digital Object Identifier (DOI)

  • 10.1016/j.chembiol.2007.02.007

PubMed ID

  • 17379147

Additional Document Info

start page

  • 321

end page

  • 8


  • 14


  • 3