Mitomycin C(MC) an antitumord rug and decarba-moylmitomycinC (DMC), ad erivative of MC lacking the carbamoyl moiety,a re DNA alkylating agents whichc an form DNA interstrand crosslinks (ICLs)b etween deoxyguanosine residues located on opposing DNA strands. MC formsp rimarily deoxyguanosine adducts with a1 "-R stereochemistry at the guanine-mitosene bond (1"-a, trans)w hereas DMC forms mainly adducts with a1 "-S stereochemistry (1"-b, cis). The crosslinking reaction is diastereospecific: trans-crosslinks are formed exclusively at CpG sequences, while cis-crosslinks are formed only at GpC sequences. Until now,o ligonucleotides containing 1"-b-deoxyguanosinea dducts or ICL at a specific site could not be synthesized, thus limiting the investigation of the role played by the stereochemical configuration at C1'' in the toxicity of thesec ompounds.H ere, a novel biomimetic synthesist oa ccess these substrates is presented. Structural proof of the adducted oligonucleotides and ICL were provided by enzymatic digestion to nucleosides, high resolution mass spectrala nalysis, CD spectroscopy and UV melting temperature studies. Finally,avirtual model of the 25-mer 1"-b ICL synthesized was createdt oe xplore the conformational space and structuralf eatures of the crosslinked duplex.

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Mitomycins are important anti‐cancer drugs. Treatment of cancer cells with mitomycins generates stereoisomeric (trans and cis) DNA interstrand crosslinks (ICLs), which prevent these highly proliferating cells from replicating. trans‐Crosslinks are formed exclusively at CpG sequences, while cis‐crosslinks are formed only at GpC sequences. This work describes a synthetic methodology to generate oligonucleotides containing the cis‐ICL (green ICL in the picture). Structural proof of the crosslinked oligonucleotide was obtained, and a virtual model of the duplex was created. More information can be found in the Full Paper by E. Champeil et al. on page 12570.