Radiolabeled albumin through SNAr of cysteines as a potential pretargeting theranostic agent
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Radiolabeled albumin through SNAr of cysteines as a potential pretargeting theranostic agent. / Fischer, Niklas H.; van den Broek, Sara I. Lopes I.; Herth, Matthias M.; Diness, Frederik.
In: RSC Advances, Vol. 12, No. 54, 2022, p. 35032-35036.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Radiolabeled albumin through SNAr of cysteines as a potential pretargeting theranostic agent
AU - Fischer, Niklas H.
AU - van den Broek, Sara I. Lopes I.
AU - Herth, Matthias M.
AU - Diness, Frederik
PY - 2022
Y1 - 2022
N2 - Human serum albumin (HSA) has been shown to be a promising tumor targeting vector and target for generating theranostics by bioconjugation. Unstable chemical conjugation to HSA via a cysteine (Cys34) by reversible Michael additions is most commonly applied for this purpose. Herein, we describe utilization of our recently developed site-selective irreversible SNAr conjugation to Cys34 using perfluorobenzene sulfonyl derivatives to introduce a trans-cyclooctene (TCO) handle. The TCO could then be bioorthogonally ligated within minutes through an inverse-electron demand Diels-Alder reaction (IEDDA) to tetrazines (Tzs) containing a radionuclide. The methodology opens up a wide range of chemistries including pretargeting, 'click-to-release' tumor selective drug delivery or ultra-fast and complete conjugation of any drug. The proof-of-principle study demonstrated that the conjugation chemistry is feasible, robust and easy to carry out, being promising for pretargeted imaging and therapy studies as well as selective drug delivery using HSA.
AB - Human serum albumin (HSA) has been shown to be a promising tumor targeting vector and target for generating theranostics by bioconjugation. Unstable chemical conjugation to HSA via a cysteine (Cys34) by reversible Michael additions is most commonly applied for this purpose. Herein, we describe utilization of our recently developed site-selective irreversible SNAr conjugation to Cys34 using perfluorobenzene sulfonyl derivatives to introduce a trans-cyclooctene (TCO) handle. The TCO could then be bioorthogonally ligated within minutes through an inverse-electron demand Diels-Alder reaction (IEDDA) to tetrazines (Tzs) containing a radionuclide. The methodology opens up a wide range of chemistries including pretargeting, 'click-to-release' tumor selective drug delivery or ultra-fast and complete conjugation of any drug. The proof-of-principle study demonstrated that the conjugation chemistry is feasible, robust and easy to carry out, being promising for pretargeted imaging and therapy studies as well as selective drug delivery using HSA.
KW - SERUM-ALBUMIN
KW - TETRAZINE
KW - CYCLOADDITIONS
KW - MECHANISMS
KW - LIGATION
U2 - 10.1039/d2ra06406e
DO - 10.1039/d2ra06406e
M3 - Journal article
C2 - 36540259
VL - 12
SP - 35032
EP - 35036
JO - RSC Advances
JF - RSC Advances
SN - 2046-2069
IS - 54
ER -
ID: 329206207