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could someone help me to decipher the structure of this molecule? I am trying to understand the structure of gemtuzumab ozogamicin: The anti-CD33 antibody is acylated with the bifunctional AcBut linker, which allows for hydrazone formation with the calicheamicin derivative. This derivative, N-acetyl-gcalicheamicin dimethylhydrazide (DMH), has a disulfide stabilized by both the two methyl groups and the calicheamicin bicyclic core, and an acetylated amino sugar. References: Joel C. Barrish, Percy H. Carter, Peter T. W. Cheng, Robert Zahler Accou... I would like to know the boundaries of AcBut linker. I got confused because in this picture it is depicted like that: enter image description here I thought that DMH was the part after the benzyl ring in the linker. Thank you in advance!

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The trick is probably the disulphide bridge which will be cleaved by reduction, once the construct has been internalized into the target cell, liberating the drug. So I'd consider everything proximal from it towards the antibody as linker structure.

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  • $\begingroup$ thank you for your answer!but this disulphide bridge does not belong to the DMH calicheamicin? $\endgroup$
    – marilu
    May 17 '20 at 12:37
  • $\begingroup$ Calicheamicin (en.wikipedia.org/wiki/Calicheamicin) has a H3C-S-S-S- group. Apparently, this modification is ok, without losing its DNA binding and cleaving functionality which is exerted by the aryl tetrasaccharide mojety and the en-diine respectively. $\endgroup$ May 17 '20 at 16:03

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