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Assemblies of D-peptides for Targeting Cell Nucleolus

preprint
submitted on 10.06.2019 and posted on 12.06.2019 by Huaimin Wang, Zhaoqianqi Feng, Weiyi Tan, Bing Xu

Selectively targeting cell nucleolus remains a challenge. Here we report the first case that D-peptides form membraneless molecular condensates with RNA for targeting cell nucleolus. A D-peptide derivative, enriched with lysine and hydrophobic residues, self-assembles to form nanoparticles, which enter cells through clathrin dependent endocytosis and mainly accumulate at cell nucleolus. Structural analogue of the D-peptide reveals that particle morphology of the assemblies, which depends on the side chain modification, favors the cellular uptake. Contrasting to those of the D-peptide, the assemblies of the corresponding L-enantiomer largely localize in cell lysosomes. Preliminary mechanism study suggests that the D-peptide nanoparticles interact with RNA to form membraneless condensates in the nucleolus, which further induces DNA damage and results in cell death. This work illustrates a new strategy for rationally designing supramolecular assemblies of D-peptides for targeting subcellular organelles.

History

Email Address of Submitting Author

whmeagle@brandeis.edu

Institution

Brandeis University

Country

United states

ORCID For Submitting Author

0000-0002-8796-0367

Declaration of Conflict of Interest

no

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in Bioconjugate Chemistry

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