Stabilization Strategies for Linear Minigastrin Analogues: Further Improvements <i>via</i> the Inclusion of Proline into the Peptide Sequence.

ABSTRACT: Minigastrin (MG) analogues, known for their high potential to target cholecystokinin-2 receptor (CCK2R) expressing tumors, have limited clinical applicability due to low enzymatic stability. By introducing site-specific substitutions within the C-terminal receptor-binding sequence, reduced metabolization and improved tumor targeting can be achieved. In this work, the influence of additional modification within the N-terminal sequence has been explored. Three novel 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-conjugated CCK2R ligands with proline substitution at different positions were synthesized. Substitution did not affect CCK2R affinity, and the conjugates labeled with indium-111 and lutetium-177 showed a high enzymatic stability in different incubation media as well

SUBMITTER: Klingler M 

PROVIDER: S-EPMC7734625 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature