NMR Studies of Co·Deglycobleomycin A2 Green and Its Complex with d(CCAGGCCTGG)

Abstract

NMR studies of the hydroperoxide form of cobalt deglycoBleomycin A2 (HOO−CodGBLM) and its complex with oligonucleotide d(CCAGGCCTGG) (1, C is the site of cleavage) are presented in an effort to establish deglycoBLM as a prototype for studies with BLM analogues, synthesized without the sugar moieties (Boger et al. Bioorg. Med. Chem. 1995, 3, 1281−1295). The structure determination of free HOO−CodGBLM has been hampered by the lack of NOE or ROE information. By direct comparison of the chemical shifts and coupling constants of HOO−CodGBLM with its glycosylated parent HOO−CoBLM, the former is shown to share many global structural features with the latter, including the nature of axial ligands (a point recently disputed by Caceres-Cortes et al. Eur. J. Biochem. 1997, 244, 818−828), the screw sense of metal-coordinating ligands, and the folding of the peptide linker region. The structure of HOO−CodGBLM bound to 1 is reported based on molecular modeling using NMR constraints (39 intermolecular and 44 intramolecu...