Synthesis of a tubugi-1-toxin conjugate by a modulizable disulfide linker system with a neuropeptide Y analogue showing selectivity for hY1R-overexpressing tumor cells.

ABSTRACT: Tubugi-1 is a small cytotoxic peptide with picomolar cytotoxicity. To improve its cancer cell targeting, it was conjugated using a universal, modular disulfide derivative. This allowed conjugation to a neuropeptide-Y (NPY)-inspired peptide [K⁴(C-βA-),F⁷,L¹⁷,P³⁴]-hNPY, acting as NPY Y1 receptor (hY1R)-targeting peptide, to form a tubugi-1-SS-NPY disulfide-linked conjugate. The cytotoxic impacts of the novel tubugi-1-NPY peptide-toxin conjugate, as well as of free tubugi-1, and tubugi-1 bearing the thiol spacer (liberated from tubugi-1-NPY conjugate), and native tubulysin A as reference were investigated by in vitro cell viability and proliferation screenings. The tumor cell lines HT-29, Colo320 (both colon cancer), PC-3 (prostate cancer), and in c

SUBMITTER: Kufka R 

PROVIDER: S-EPMC6334802 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature