Kilpatrick Townsend & Stockton LLP
Multi-valent poly-Ubl chain inhibitors and methods of use
A composition used to develop a reagent for investigating Ubl-modifications in cellular functions and in the treatment of cancer is provided. The composition comprises gold nanoparticle (AuNP)-ligand conjugates that include at least two components: gold nanoparticles (AuNPs) and modified ubiquitin- or ubiquitin-like interacting motif (UIM or ULIM) mimetics. In one embodiment, the modified ULM mimetic is a modified SUMO interaction motif (SIM) mimetic. According to the embodiments described herein, the compound inhibits ubiquitin- or ubiquitin-like protein (Ubl)-mediated protein-protein interactions and sensitizes cells to ionizing radiation. The modified UIM and ULIM mimetics may be conjugated to the AuNP such that each AuNP is conjugated to a plurality of modified UIM or ULIM mimetics. The modified ULIM mimetics may be conjugated to the AuNP via a thiol group.
City of Hope
A B A C A C C C
A61K B82Y A61K C07K A61K C07K C07K C07D
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Yuelong David Angela L. Yuan Yang Yi-Jia
Ma Horne Perkins-Harki Chen Su Li