Helix-Guarded Molecular Clips for Cell-Free DNA Scavenging and Treatment of Systemic Lupus Erythematosus DOI
Yang Zhou, Huan Ye, Yi Yu

et al.

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 11, 2025

Immune disorders induced by cell-free DNA (cfDNA) account for the incidence and deterioration of systemic lupus erythematosus (SLE). Scavenging cfDNA using cationic polymers represents a promising modality SLE management. However, they bind mainly via electrostatic interaction, which would result in an undesired discharge captured upon competitive replacement negatively charged serum/intracellular components. Inspired natural recognition mechanism biomacromolecules spatial matching, we herein developed library dendrimer-templated, spherical, α-helical, guanidine-rich polypeptides as molecular clips scavenging. Upon optimization polypeptide length density on dendrimer surface, top-performing G3-8 was identified, could tightly confine within cavity between adjacent, rod-like α-helices. As thus, helical but not random-coiled analogue D,L-G3-8 enabled robust scavenging under serum-rich conditions to inhibit TLR9 activation inflammation. In mice, i.v. injected efficiently prevented organ failure inhibited inflammation cfDNA. This study provides enlightened strategy stably scavenge may shift current paradigm

Language: Английский

Helix-Guarded Molecular Clips for Cell-Free DNA Scavenging and Treatment of Systemic Lupus Erythematosus DOI
Yang Zhou, Huan Ye, Yi Yu

et al.

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 11, 2025

Immune disorders induced by cell-free DNA (cfDNA) account for the incidence and deterioration of systemic lupus erythematosus (SLE). Scavenging cfDNA using cationic polymers represents a promising modality SLE management. However, they bind mainly via electrostatic interaction, which would result in an undesired discharge captured upon competitive replacement negatively charged serum/intracellular components. Inspired natural recognition mechanism biomacromolecules spatial matching, we herein developed library dendrimer-templated, spherical, α-helical, guanidine-rich polypeptides as molecular clips scavenging. Upon optimization polypeptide length density on dendrimer surface, top-performing G3-8 was identified, could tightly confine within cavity between adjacent, rod-like α-helices. As thus, helical but not random-coiled analogue D,L-G3-8 enabled robust scavenging under serum-rich conditions to inhibit TLR9 activation inflammation. In mice, i.v. injected efficiently prevented organ failure inhibited inflammation cfDNA. This study provides enlightened strategy stably scavenge may shift current paradigm

Language: Английский

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