biostudies-literatureUnknown15Kufka RTubugi-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 cBeilstein journal of organic chemistry96-105https://www.ebi.ac.uk/biostudies/studies/S-EPMC6334802biostudies-literatureSynthesis of a tubugi-1-toxin conjugate by a modulizable disulfide linker system with a neuropeptide Y analogue showing selectivity for hY1R-overexpressing tumor cells.PMC6334802Weber LKaluđerovic GNRichter WWessjohann LAKufka RRennert RfalseSynthesis of a tubugi-1-toxin conjugate by a modulizable disulfide linker system with a neuropeptide Y analogue showing selectivity for hY1R-overexpressing tumor cells.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 c2019-01-01T00:00:00Z20192026-07-16T17:32:27.89Z2025-05-29T19:42:06.974ZS-EPMC63348023068004410.3762/bjoc.15.11