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Updated: Aug 14, 2026

Sequence-specific Labeling of Nucleic Acids and Proteins with Methyltransferases and Cofactor Analogues
Published on: November 22, 2014
N-methyl threonine analogues of deglycobleomycin A2: synthesis and evaluation
1Department of Chemistry, Scripps Research Institute, La Jolla, CA 92037, USA.
Abstract:
The synthesis of 5 and its D-allo-threonine epimer 6 and the comparison of their DNA cleavage efficiency and selectivity with that of deglycobleomycin A2 (3) are detailed. The studies illustrate that N-methylation of the L-threonine subunit within deglycobleomycin A2 dramatically reduces the DNA cleavage efficiency (10-15-fold), weakens and nearly abolishes the inherent DNA cleavage selectivity, but has little effect on the inherent oxidation capabilities of the activated Fe(III) complexes. The results are consistent with a previously unrecognized prominent role for the threonine NH and the potential importance of a hydrogen bond to the Fe(III) hydroperoxide complex of bleomycin or a subsequent activated complex implicated in recent structural models.
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