Delving into the Latest Updates on R-9 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

RBBP4

Mechanism

RBBP4 inhibitors(RB binding protein 4, chromatin remodeling factor inhibitors)

Therapeutic Areas

NeoplasmsSkin and Musculoskeletal Diseases

Active Indication

Triple Negative Breast Cancer

Inactive Indication-

Originator Organization

Virginia Commonwealth University

Active Organization

Virginia Commonwealth University

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

AbstractArginine‐rich cell‐penetrating peptides (CPPs) have emerged as valuable tools for the intracellular delivery of bioactive molecules, but their membrane perturbation during cell penetration is not fully understood. Here, nona‐arginine (R9)‐mediated membrane reorganization that facilitates the translocation of peptides across laterally heterogeneous membranes is directly visualized. The electrostatic binding of cationic R9 to anionic phosphatidylserine (PS)‐enriched domains on a freestanding lipid bilayer induces lateral lipid rearrangements; in particular, in real‐time it is observed that R9 fluidizes PS‐rich liquid‐ordered (Lo) domains into liquid‐disordered (Ld) domains, resulting in the membrane permeabilization. The experiments with giant unilamellar vesicles (GUVs) confirm the preferential translocation of R9 through Ld domains without pore formation, even when Lo domains are more negatively charged. Indeed, whenever R9 comes into contact with negatively charged Lo domains, it dissolves the Lo domains first, promoting translocation across phase‐separated membranes. Collectively, the findings imply that arginine‐rich CPPs modulate lateral membrane heterogeneity, including membrane fluidization, as one of the fundamental processes for their effective cell penetration across densely packed lipid bilayers.

100 Deals associated with R-9

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