Metabolism of an alkyl polyamine analog by a polyamine oxidase from the microsporidian Encephalitozoon cuniculi

Cyrus J. Bacchi, Nigel Yarlett, Evangeline Faciane, Xiangdong Bi, Donna Rattendi, Louis M. Weiss, Patrick M. Woster

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Encephalitozoon cuniculi is a microsporidium responsible for systemic illness in mammals. In the course of developing leads to new therapy for microsporidiosis, we found that a bis(phenylbenzyl)3-7-3 analog of spermine, 1,15-bis{N-[o-(phenyl)benzylamino}-4,12-diazapentadecane (BW-1), was a substrate for an E. cuniculi amine oxidase activity. The primary natural substrate for this oxidase activity was N′-acetylspermine, but BW-1 had activity comparable to that of the substrate. As the sole substrate, BW-1 gave linear reaction rates over 15 min and Km of 2 μM. In the presence of N′-acetylspermine, BW-1 acted as a competitive inhibitor of oxidase activity and may be a subversive substrate, resulting in increased peroxide production. By use of 13C-labeled BW-1 as a substrate and nuclear magnetic resonance analysis, two products were determined to be oxidative metabolites, a hydrated aldehyde or dicarboxylate and 2(phenyl)benzylamine. These products were detected after exposure of 13C-labeled BW-1 to E. cuniculi preemergent spore preparations and to uninfected host cells. In previous studies, BW-1 was curative in a rodent model of infection with E. cuniculi. The results in this study demonstrate competitive inhibition of oxidase activity by BW-1 and support further studies of this oxidase activity by the parasite and host.

Original languageEnglish (US)
Pages (from-to)2599-2604
Number of pages6
JournalAntimicrobial Agents and Chemotherapy
Volume53
Issue number6
DOIs
StatePublished - Jun 2009

Fingerprint

Encephalitozoon cuniculi
Polyamines
Oxidoreductases
Unclassified Microsporidia
Microsporidiosis
Spermine
Peroxides
Spores
Aldehydes
Amines
Mammals
Rodentia
Parasites
Magnetic Resonance Spectroscopy
polyamine oxidase
Infection

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology
  • Infectious Diseases

Cite this

Metabolism of an alkyl polyamine analog by a polyamine oxidase from the microsporidian Encephalitozoon cuniculi. / Bacchi, Cyrus J.; Yarlett, Nigel; Faciane, Evangeline; Bi, Xiangdong; Rattendi, Donna; Weiss, Louis M.; Woster, Patrick M.

In: Antimicrobial Agents and Chemotherapy, Vol. 53, No. 6, 06.2009, p. 2599-2604.

Research output: Contribution to journalArticle

Bacchi, Cyrus J. ; Yarlett, Nigel ; Faciane, Evangeline ; Bi, Xiangdong ; Rattendi, Donna ; Weiss, Louis M. ; Woster, Patrick M. / Metabolism of an alkyl polyamine analog by a polyamine oxidase from the microsporidian Encephalitozoon cuniculi. In: Antimicrobial Agents and Chemotherapy. 2009 ; Vol. 53, No. 6. pp. 2599-2604.
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