Examination of the impact molecular charge has on NTSR1-targeted agents incorporated with cysteine protease inhibitors.

ABSTRACT: Our laboratory has previously reported a strategy of employing cysteine cathepsin (CC) inhibitors as adduct forming, trapping agents to extend the tumor residence time of neurotensin receptor subtype 1 (NTSR1)-targeted radiopharmaceuticals. As a follow-up, we herein report a small library of CC trapping agent (CCTA)-incorporated, NTSR1-targeted conjugates with structural modifications that reduce the number of charged functional groups for both the CCTA and the peptide targeting sequence. These modifications were pursued to reduce the renal uptake and increase the translational potential of the CCTA-incorporated, NTSR1-targeted agents as radiotherapeutics. The biological performance of these constructs was examined using a battery of in vitro and in vivo studies employing the NTSR1-positiv

SUBMITTER: Fan W 

PROVIDER: S-EPMC9007894 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature