Abstract
Adenosine analogues bearing either 5′-aziridine or 5′-N-mustard electrophiles are methyltransferase-dependent DNA alkylating agents. We present here a novel synthetic cofactor bearing a pendant 5′-amino acid N-mustard. Unlike previously studied synthetic cofactors, this material is very efficiently used by the natural product biosynthetic enzyme rebeccamycin methyltransferase (RebM) to generate a number of new rebeccamycin analogues. These data promote the notion that natural product methyltransferases can be used with non-natural cofactors to enhance the molecular diversity of natural product analogues for drug discovery. To our knowledge, this is the first documentation of a biological methyltransferase, other than DNA methyltransferases, that can exploit such synthetic cofactors.
Original language | English |
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Pages (from-to) | 2760-2761 |
Number of pages | 2 |
Journal | Journal of the American Chemical Society |
Volume | 128 |
Issue number | 9 |
DOIs | |
State | Published - Mar 8 2006 |
ASJC Scopus subject areas
- Catalysis
- Chemistry (all)
- Biochemistry
- Colloid and Surface Chemistry