Guanidino-G-Clamp-PNA

Guanidino-G-Clamp-PNA is a highly effective sequence-specific RNA binding and gene silencing agent. It targets specific sequences, such as miR-155 or transthyretin protein (TTR) mRNA, through precise base pairing. By reducing microRNA activity, it modulates tumor-associated signaling pathways, while also using steric hindrance effects to inhibit the translation of harmful proteins. Guanidino-G-Clamp-PNA can stabilize DNA/RNA duplexes and induce apoptosis, thereby inhibiting tumor growth. It can be conjugated with targeting ligands to enhance tissue-specific delivery and reduce adverse effects in vivo, and it can improve splice-modulation efficacy when incorporated into other oligonucleotide platforms, such as [PMO]. This compound is useful for researching various diseases, including diffuse large B-cell lymphoma and hereditary transthyretin-related amyloidosis.

Guanidino-G-Clamp-PNA at 4 μM cGPNA2 for 48 hours inhibits miR-155 in U2932 diffuse large B-cell lymphoma cells, upregulating tumor suppressor targets and downregulating oncogene expression. It similarly affects SUDHL-5 cells, strongly suppressing miR-155 and regulating expression of downstream tumor suppressor and oncogenes. Guanidino-G-Clamp-PNA at concentrations of 1-4 μM cGPNA5 over 24 hours reduces TTR mRNA levels in HepG2 cells in a dose-dependent manner, achieving a 69% knockdown at 4 μM. In U2932 and SUDHL-5 cells, 0.5-4 μM cGPNA2 exposure for 48 hours decreases cell viability, inducing apoptosis dose-dependently, with cell viability dropping by ≥60% at 4 μM and approximately 20% of U2932 cells in late apoptosis. Additionally, 2-4 μM cGPNA5 in rabbit reticulocyte lysate cell-free systems for 3 hours under conditions of 37°C and mRNA to reagent ratio of 1:4 reduces TTR protein levels by 62% after pre-incubation.