DNA-Interactive Drugs: Mitomycin C


Name Mitomycin C 
mutamycin 
mitocin C
CAS#  50-07-7
MW 334.33
Binding Mode Reduced drug forms monofunctional covalent adducts and bifunctional interstrand crosslinks [Iyer, 1964] to N2-G [Tomasz, 1986] located in minor groove.  Acid activated-mitomycin forms adduct with N7-G [Tomasz, 1987] in major groove.
Site Specificity Adducts to guanines.  5'-CG-3'  required for interstrand crosslink formation, and 5'-GG-3' required for intrastrand crosslinks.  Preferred monofunctional site is 5'-CGN-3' > 5'-GGN-3', N is (C>T>G>A) according to study with oligonucleotides [Kumar, 1992].
Effect on DNA Monoadduct and interstrand crosslink do not significantly alter DNA conformation [Tomasz, 1987]; however, G-G intrastrand crosslink results in DNA bending [Kumar, 1992].
Preparation and Use Purple solution.  Requires reduction for covalent bonding to DNA.  Mitomycin C that is reduced and reoxidized is inactive [Iyer, 1964].  Activation with Na2S2O4 results primarily in G-G interstrand crosslinks, while enzymatic or  Pt-catalyzed reduction results in monoadduct formation [Tomasz, 1987]. 
 
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Please direct all comments to: Jack Welch, M.D., Ph.D.
Last Modified August 1, 1998Last modification: August 10, 1998