% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Marker:298993,
      author       = {T. Marker$^*$ and R. Steimbach$^*$ and C. Perez-Borrajero
                      and M. Luzarowski and E. Hartmann and S. Schleich$^*$ and D.
                      Pastor-Flores$^*$ and E. Espinet and A. Trumpp$^*$ and A.
                      Teleman$^*$ and F. Gräter and B. Simon and A. Miller$^*$
                      and T. Dick$^*$},
      title        = {{S}ite-specific activation of the proton pump inhibitor
                      rabeprazole by tetrathiolate zinc centres.},
      journal      = {Nature chemistry},
      volume       = {17},
      number       = {4},
      issn         = {1755-4330},
      address      = {London},
      publisher    = {Nature Publishing Group},
      reportid     = {DKFZ-2025-00403},
      pages        = {507-517},
      year         = {2025},
      note         = {DKFZ-ZMBH Alliance / 2025 Apr;17(4):507-517 /#EA:
                      A160#LA:A160#},
      abstract     = {Proton pump inhibitors have become top-selling drugs
                      worldwide. Serendipitously discovered as prodrugs that are
                      activated by protonation in acidic environments, proton pump
                      inhibitors inhibit stomach acid secretion by covalently
                      modifying the gastric proton pump. Despite their widespread
                      use, alternative activation mechanisms and potential target
                      proteins in non-acidic environments remain poorly
                      understood. Employing a chemoproteomic approach, we found
                      that the proton pump inhibitor rabeprazole selectively forms
                      covalent conjugates with zinc-binding proteins. Focusing on
                      DENR, a protein with a C4 zinc cluster (that is, zinc
                      coordinated by four cysteines), we show that rabeprazole is
                      activated by the zinc ion and subsequently conjugated to
                      zinc-coordinating cysteines. Our results suggest that drug
                      binding, activation and conjugation take place rapidly
                      within the zinc coordination sphere. Finally, we provide
                      evidence that other proton pump inhibitors can be activated
                      in the same way. We conclude that zinc acts as a Lewis acid,
                      obviating the need for low pH, to promote the activation and
                      conjugation of proton pump inhibitors in non-acidic
                      environments.},
      cin          = {A160 / A390 / B140 / A010 / HD01},
      ddc          = {540},
      cid          = {I:(DE-He78)A160-20160331 / I:(DE-He78)A390-20160331 /
                      I:(DE-He78)B140-20160331 / I:(DE-He78)A010-20160331 /
                      I:(DE-He78)HD01-20160331},
      pnm          = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
      pid          = {G:(DE-HGF)POF4-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:39979415},
      doi          = {10.1038/s41557-025-01745-8},
      url          = {https://inrepo02.dkfz.de/record/298993},
}