Complexation of antimony (SbV) with guanosine 5′-monophosphate and guanosine 5′-diphospho-D-mannose: Formation of both mono- and bis-adducts

Yi Chai, Siucheong Yan, Iris L K Wong, Ming Cheung Chow, Hongzhe Sun

Research output: Journal article publicationJournal articleAcademic researchpeer-review

25 Citations (Scopus)

Abstract

In spite of the extensive use of pentavalent antimony chemotherapy, the mechanism of its anti-leishmania action is still not clear. Here, we report the interactions of SbV, including the clinically used drug stibogluconate, with guanosine 5′-monophosphate (5′-GMP) and guanosine 5′-diphospho-d-mannose (5′-GDP-mannose) in aqueous solution. The deprotonated hydroxyl groups (-OH) of the ribose ring are shown to be the binding site for SbV, probably via chelation. Both mono- and bis-adducts were formed as determined by NMR, high performance liquid chromatography (HPLC) and electrospray ionization mass spectrometry (ESI-MS), and both of them are stable in the pH range of 4 to around 9.5. The formation of the mono-adduct (k1= 1.67 × 10-3and 3.43 × 10-3mM-1min-1for Sb(5′-GMP) and Sb(5′-GDP-mannose), respectively, at 298 K) was 10-fold faster than that of the bis-adduct (k2= 0.16 × 10-3and 0.21 × 10-3mM-1min-1, for Sb(5′-GMP)2and Sb(5′-GDP-mannose)2, respectively), and the mono-adduct was the major species in solution with the [bis-adduct]/[mono- adduct] < 0.5. The reactions of stibogluconate with 5′-GMP and 5′-GDP-mannose were slower than that of antimonate under similar conditions.
Original languageEnglish
Pages (from-to)2257-2263
Number of pages7
JournalJournal of Inorganic Biochemistry
Volume99
Issue number12
DOIs
Publication statusPublished - 1 Dec 2005

Keywords

  • Antimony
  • ESI-MS
  • Guanosine 5′-diphospho-d-mannose
  • Guanosine 5′-monophosphate
  • Leishamania
  • NMR

ASJC Scopus subject areas

  • Biochemistry
  • Inorganic Chemistry

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