Trifluoromethylketones as possible transition state analog inhibitors of juvenile hormone esterase

Bruce D. Hammock, Keith D. Wing, James McLaughlin, Victor M. Lovell, Thomas C. Sparks

Research output: Contribution to journalArticle

103 Citations (Scopus)

Abstract

A series of compounds containing the trifluoromethylketone group have been synthesized utilizing either a modified Grignard procedure or by reacting selected aliphatic bromides or tosylates with the Collman reagent [Na2Fe(CO)4]. When tested in vitro as inhibitors of crude juvenile hormone esterase from the hemolymph of the cabbage looper, Trichoplusia ni (Noctuidae), the most active compounds were trifluoromethylketones possessing either a juvenoid-like structure or a straight aliphatic chain. The logarithm of the inhibitory potency of the aliphatic compounds was proportional to their chain length, up to 1,1,1-trifluorotetradecan-2-one (I50 = 1 × 10-7 M). This powerful inhibition was found to be highly selective for JHE, reversible, competitive by Lineweaver-Burk analysis, and was characterized by high affinity of the inhibitor for the esterase (Ki = 3.2 × 10-9 M, Km JH III = 2 × 10-7 M). Other trifluoromethylketones were shown to be inhibitors of T. ni α-naphthylacetate esterase and bovine trypsin. By analogy with the mechanism of trypsin action, trifluoromethylketones are probably potent inhibitors due to their resemblance to a tetrahedral transition state on the reaction coordinate to the acylated enzyme.

Original languageEnglish (US)
Pages (from-to)76-88
Number of pages13
JournalPesticide Biochemistry and Physiology
Volume17
Issue number1
DOIs
StatePublished - 1982

Fingerprint

Trichoplusia
juvenile hormone esterase
Esterases
Noctuidae
esterases
Trypsin
trypsin
juvenile hormone analogs
Trichoplusia ni
Hemolymph
Brassica
Carbon Monoxide
bromides
Bromides
Chain length
hemolymph
cattle
Enzymes
enzymes

ASJC Scopus subject areas

  • Agronomy and Crop Science
  • Biochemistry
  • Physiology

Cite this

Trifluoromethylketones as possible transition state analog inhibitors of juvenile hormone esterase. / Hammock, Bruce D.; Wing, Keith D.; McLaughlin, James; Lovell, Victor M.; Sparks, Thomas C.

In: Pesticide Biochemistry and Physiology, Vol. 17, No. 1, 1982, p. 76-88.

Research output: Contribution to journalArticle

Hammock, Bruce D. ; Wing, Keith D. ; McLaughlin, James ; Lovell, Victor M. ; Sparks, Thomas C. / Trifluoromethylketones as possible transition state analog inhibitors of juvenile hormone esterase. In: Pesticide Biochemistry and Physiology. 1982 ; Vol. 17, No. 1. pp. 76-88.
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