Aptamer‐SH2 superbinder‐based targeted therapy for pancreatic ductal adenocarcinoma

Abstract

Schematic diagram of XQ-2d-His-SH2 CM-(Arg)9 in PDAC cells and PSCs. XQ-2d-His-SH2 CM-(Arg)9 could bind and penetrate into PSCs, inactivate PSCs, and decrease ECM secretion. XQ-2d-His-SH2 CM-(Arg)9 could reach tumor tissues, recognize, and enter into the PDAC cells. XQ-2d-His-SH2 CM-(Arg)9 could function as a broad-spectrum inhibitor via capturing pY-containing proteins and blocking multitude pY-based signaling pathways in PDAC cells.

Blockade of phosphotyrosine pathways suggesting SH2 superbinder as a novel therapy for pulmonary fibrosis

“…Our results showed significant inhibitory effect of SH2 superbinder on pY levels of RTKs downstream proteins such as GAB1, GRB2 and SHC. In lung fibroblasts cells, SH2 superbinder could specifically restrain pY levels of EGFR, while in our previous study on pancreatic ductal adenocarcinoma cells, SH2 superbinder suppressed pY levels of VEGFR, EGFR and IGFR 51 . We think that there is a feedback regulation mechanism between pY levels of RTKs and SH2 superbinder in different cell types and future study should be done to clarify the mechanism.…”

“…SH2 superbinder with triple AA mutants was designed to target this specific binding process 14 . In vitro and in vivo experiments showed that SH2 superbinder had stronger affinity than natural SH2 domain to pY 14 , 51 . In another study, we found that GST-SH2 TrM also restrained TGF-β1-induced differentiation of fibroblasts, despite that the receptor of TGF-β is serine/threonine kinase and the signal transduction is dependent on pS/pT.…”

Advances in screening, synthesis, modification, and biomedical applications of peptides and peptide aptamers

“…In vivo, experiments involve the injection of peptides/PAs into cells or animal models to further evaluate their interactions with target substances. For instance, Liu et al 34 employed PAs as carriers and coupled them with drug molecules to form aptamer‐SH2 superbinder‐(Arg)9 conjugates. These conjugates demonstrated enhanced cellular uptake efficacy and were validated in tumor‐bearing mice, resulting in the inhibition of cancer cell growth and metastasis.…”

Record Resolution of Nanometal Surface Energy Transfer Optical Nanoruler Projects 3D Spatial Configuration of Aptamers on a Living Cell Membrane

“…10,13 Even a few studies reported an unclear structure of XQ-2d. 14 X-ray crystallography or nuclear magnetic resonance spectroscopy has been used to reveal aptamers' conformation when binding to a transcription factor (NF-κB p50) homodimer, 15 prostatespecific membrane antigen, 16 thrombin protein, 17 and thrombin factor (FXa); 18 however, these processes require an extraction step, and this may lead to a variation in the conformation of ligands. 19 It is attractive to develop a method for the in situ decryption of ligands' conformation without using expensive instruments, expert professional operators, derivatization treatments, or large amounts of organic solvents.…”

“…Previously, we studied the binding of an XQ-2d aptamer to the overexpressed CD71 receptor in PL45 cells . However, the conformation of XQ-2d in solution was mostly predicted based on its secondary structure. , Even a few studies reported an unclear structure of XQ-2d . X-ray crystallography or nuclear magnetic resonance spectroscopy has been used to reveal aptamers’ conformation when binding to a transcription factor (NF-κB p50) homodimer, prostate-specific membrane antigen, thrombin protein, and thrombin factor (FXa); however, these processes require an extraction step, and this may lead to a variation in the conformation of ligands .…”