Enhanced activity of an insecticidal protein, trypsin modulating oostatic factor (TMOF), through conjugation with aliphatic polyethylene glycol

Autor(es): Jeffers, Laura A.; Shen, Hongyan; Khalil, Sayed; Bissinger, Brooke W.; Brandt, Alan; Gunnoe, T. Brent; Roe, R. Michael


Resumo: 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. (C) 2011 Society of Chemical Industry


Palavras-Chave: Trypsin modulating oostatic factor; TMOF; PEGylation; Polyethylene glycol; Mosquito; Tobacco budworm; Cotton bollworm; Protein delivery


Imprenta: Pest Management Science, v. 68, n. 1, p. 49-59, 2012


Identificador do objeto digital: 10.1002/ps.2219


Descritores: Aedes aegypti - Biochemistry ; Aedes aegypti - Biosynthesis ; Aedes aegypti - Public health


Data de publicação: 2012