Hi Kanth,
We did not perform the pre-conditioning in the original Mei et al paper. Among other things, we didn't find the ref 43 that Felix cited (
https://cancerres.aacrjournals.org/cont ... /3913.long).
Based on what Felix wrote, though, it doesn't seem to be *required*, but I don't think it would be bad for the conjugation. In fact, in the discussion in ref 43, there's this comment: "For example, a crystallographic study of cisplatin and carboplatin binding to histidines of hen egg-white lysozyme found one platinum bound to His15 when cisplatin was dissolved in aqueous medium. When dissolved in DMSO, two platinum atoms bound to His15, leading to the conclusion that DMSO could facilitate platinum-protein binding (49)."
I think some of it comes down to the fact that the *cytotoxicity* of cisplatin and the *chemical reactivity* of cisplatin are technically different things. At least a large part of the *cytotoxicity* is due to the formation of crosslinks, which is dependent on the cis structure and replacement of both Cl ligands by something else (often the exocyclic amines of Guanines, to form G1-NH2-mu(Pt-(NH3)2)-NH2-G2, where mu means it's bridging between the two Guanines, and the two NH3 are remaining ligands from the cisplatin (cis-PtCl2(NH3)2) after the chlorides are displaced.
So, in order to form a *crosslink*, you need both Cl's (technically, inside the cell the Cl's can be replaced by H2O ligands, but you still need both Cl's to start with). Therefore, if you don't have that due to ligand replacement, you can't form a crosslink.
However, to just *label* something with cisplatin, you just need *at least one* cisplatin ligand to be replaced by a biological amine (or to a lesser extent, thiol).....it doesn't matter whether it forms a crosslink (2 ligands) or whether it forms a terminal/pendant adduct (1 ligand). I think the preconditioning in the DMSO helps reduce the cytotoxicity just to make it friendlier to handle in the lab.....
Mike