T2AA, a proliferating cell nuclear antigen (PCNA) inhibitor, disrupts protein-protein interactions between PCNA and both a PIP-box-containing peptide (IC50= 1 μM) and full-length p21, reducing cellular colocalization of PCNA with DNA polymerase δ. This compound effectively inhibits DNA replication and cell proliferation in U2OS and HeLa cells in a concentration-dependent manner, additionally inducing S phase cell cycle arrest at a 20 μM concentration. Furthermore, T2AA enhances DNA double strand break formation alongside cisplatin in a neutral comet assay and augments cisplatin-induced reductions in clonogenic survival in HeLa and U2OS cells.
N-(Propargyl-PEG2)-N-Boc-PEG3-t-butyl ester is a polyethylene glycol (PEG)-based linker employed for the synthesis of proteolysis-targeting chimeras (PROTACs) [1].
Azido-PEG2-t-butyl ester is a PEG derivative containing a t-butyl ester and an azide group. The hydrophilic PEG spacer increases solubility in aqueous media. Under acidic conditions, the t-butyl protected carboxyl group can be deprotected.
Thiol-PEG2-t-butyl ester is a PEG-based linker for PROTACs which joins two essential ligands, crucial for forming PROTAC molecules. This linker enables selective protein degradation by leveraging the ubiquitin-proteasome system within cells.