title: Enhanced activity of an insecticidal protein, trypsin modulating oostatic factor (TMOF), through conjugation with aliphatic polyethylene glycol.
abstract: BACKGROUND
  Trypsin modulating oostatic factor (TMOF), a decapeptide (Tyr-Asp-Pro-Ala-Pro(6)) isolated from the ovaries of the adult yellow fever mosquito, Aedes aegypti, regulates trypsin biosynthesis. TMOF per os is insecticidal to larval mosquitoes and a good model for the development of technologies to enhance protein insecticide activity by reduced catabolism and/or enhanced delivery to the target.
  
  
  RESULTS
  TFA-TMOF-K (TFA = trifluoro acetyl) allowed the specific conjugation of monodispersed, aliphatic polyethylene glycol (PEG) to the amino group of lysine-producing TMOF-K-methyl(ethyleneglycol)(7)-O-propionyl (TMOF-K-PEG(7) P). The addition of lysine to TMOF reduced its per os larval mosquitocidal activity relative to the parent TMOF, but conjugation of TMOF-K with methyl(ethyleneglycol)(7)-O-propionyl increased its toxicity 5.8- and 10.1-fold above that of TMOF and TMOF-K for Ae. aegypti. Enhanced insecticidal activity was also found for larval Ae. albopictus and for neonates of Heliothis virescens and Heliocoverpa zea. Only TMOF-K was found by MS/MS in the hemolymph for H. virescens fed on TMOF-K-PEG(7) P. No TMOF, TMOF-K or PEGylated TMOF-K was detected in the hemolymph after topical applications.
  
  
  CONCLUSIONS
  This research suggests that aliphatic PEG polymers can be used as a new method for increasing the activity of insecticidal proteins.
authors.affiliation: Department of Entomology, North Carolina State University, Raleigh, NC, USA.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Jeffers
authors.forename: Hongyan
authors.initials: H
authors.lastname: Shen
authors.forename: Sayed
authors.initials: S
authors.lastname: Khalil
authors.forename: Brooke W
authors.initials: BW
authors.lastname: Bissinger
authors.forename: Alan
authors.initials: A
authors.lastname: Brandt
authors.forename: T Brent
authors.initials: TB
authors.lastname: Gunnoe
authors.forename: R Michael
authors.initials: RM
authors.lastname: Roe
mesh_terms: D000330:Aedes / Q000187:drug effects* / Q000254:growth & development; D000818:Animals; D007306:Insecticides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007814:Larva / Q000187:drug effects / Q000254:growth & development; D009036:Moths / Q000187:drug effects; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000737:chemistry*
chemical_list: D007306:Insecticides; D009842:Oligopeptides; C065612:Peptide oostatic hormone; D011092:Polyethylene Glycols