Structures of cobalt(III)-pepleomycin and cobalt(III)-deglycopepleomycin (green fonns) determined by NMR studies

Janet Caceres-Cortes, Hiroshi Sugiyama, Kenji Ikudome, Isao Saito, Andrew H.J. Wang

Research output: Contribution to journalArticlepeer-review

41 Citations (Scopus)

Abstract

Pepleomycin (PEP) is a metalloglycopeptide that has stronger anticancer activity and less pulmonary toxicity than bleomycin (BLM). PEP, like BLM, exerts its action by binding to and degrading DNA in the presence of oxygen and certain metals. Obtaining detailed structural information of PEP and PEP-DNA complexes is crucial to understanding its anticancer activity. The structures of two green forms of cobalt-PEP species, HO2--Co(III)-PEP (denoted CoPEP) and deglycosylated HO2--Co(III)-PEP (denoted CodPEP) have been obtained by NOE restrained refinements. Earlier studies of the related HO2--Co(III)-BLM A2 proposed that two chiral conformers (form A or B) could exist with either the β-aminoalanine primary amine (A,NH2) or the mannose carbamoyl nitrogen (M,NH2) as the axial ligand. Analysis of our NOESY data shows convincingly that form A is the most probable conformer with the mannose carbamoyl M,NH2 and the β-aminoalanine primary amine A,NH2 as the axial ligands in CoPEP and CodPEP, respectively. The NOE cross-peaks resulting from the interactions between the N-terminus (i.e., the metal-binding domain) and the C-terminus of CoPEP and CodPEP have similar patterns, suggesting that they both adopt compact structures with the bithiazole group folded back over the N-terminus.

Original languageEnglish
Pages (from-to)818-828
Number of pages11
JournalEuropean Journal of Biochemistry
Volume244
Issue number3
DOIs
Publication statusPublished - 1997
Externally publishedYes

Keywords

  • Deglycosylated pepleomycin
  • DNA
  • Pepleomycin
  • Solution structure
  • Two-dimensional NMR

ASJC Scopus subject areas

  • Biochemistry

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