Assemblies of D-Peptides for Targeting Cell Nucleolus

Overview

Journal Bioconjug Chem

Publisher American Chemical Society

Specialty Biochemistry

Date 2019 Sep 25

PMID 31550136

Citations 14

Authors

Huaimin Wang

Zhaoqianqi Feng

Weiyi Tan

Bing Xu

Affiliations

Soon will be listed here.

Abstract

Selectively targeting the cell nucleolus remains a challenge. Here, we report the first case in which 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 the cell nucleolus. A structural analogue of the d-peptide reveals that the particle morphology of the assemblies, which depends on the side chain modification, favors the cellular uptake. In contrast 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.

Citing Articles

Role of Functionalized Peptides in Nanomedicine for Effective Cancer Therapy.

Kim K, Park M Biomedicines. 2024; 12(1).

PMID: 38255307 PMC: 10813321. DOI: 10.3390/biomedicines12010202.

Engineering of antimicrobial peptide fibrils with feedback degradation of bacterial-secreted enzymes.

Wang F, Xia W, Zhang M, Wu R, Song X, Hao Y Chem Sci. 2023; 14(39):10914-10924.

PMID: 37829030 PMC: 10566480. DOI: 10.1039/d3sc01089a.

-Acetylation of Biodegradable Supramolecular Peptide Nanofilaments Selectively Enhances Their Proteolytic Stability for Targeted Delivery of Gold-Based Anticancer Agents.

Marciano Y, Nayeem N, Dave D, Ulijn R, Contel M ACS Biomater Sci Eng. 2023; 9(6):3379-3389.

PMID: 37192486 PMC: 10699682. DOI: 10.1021/acsbiomaterials.3c00312.

Designing bioresponsive nanomaterials for intracellular self-assembly.

Chagri S, Ng D, Weil T Nat Rev Chem. 2023; 6(5):320-338.

PMID: 37117928 PMC: 8972907. DOI: 10.1038/s41570-022-00373-x.

Molecular dynamics study of the internalization of cell-penetrating peptides containing unnatural amino acids across membranes.

Gimenez-Dejoz J, Numata K Nanoscale Adv. 2022; 4(2):397-407.

PMID: 36132688 PMC: 9419563. DOI: 10.1039/d1na00674f.

References

Feng Z, Wang H, Wang S, Zhang Q, Zhang X, Rodal A . Enzymatic Assemblies Disrupt the Membrane and Target Endoplasmic Reticulum for Selective Cancer Cell Death. J Am Chem Soc. 2018; 140(30):9566-9573. PMC: 6070399. DOI: 10.1021/jacs.8b04641. View

Feng Z, Zhang T, Wang H, Xu B . Supramolecular catalysis and dynamic assemblies for medicine. Chem Soc Rev. 2017; 46(21):6470-6479. PMC: 5662491. DOI: 10.1039/c7cs00472a. View

Raska I, Shaw P, Cmarko D . Structure and function of the nucleolus in the spotlight. Curr Opin Cell Biol. 2006; 18(3):325-34. DOI: 10.1016/j.ceb.2006.04.008. View

Kwon I, Xiang S, Kato M, Wu L, Theodoropoulos P, Wang T . Poly-dipeptides encoded by the C9orf72 repeats bind nucleoli, impede RNA biogenesis, and kill cells. Science. 2014; 345(6201):1139-45. PMC: 4459787. DOI: 10.1126/science.1254917. View

Wei X, Zhan C, Shen Q, Fu W, Xie C, Gao J . A D-peptide ligand of nicotine acetylcholine receptors for brain-targeted drug delivery. Angew Chem Int Ed Engl. 2015; 54(10):3023-7. DOI: 10.1002/anie.201411226. View

Shimada T, Lee S, Bates F, Hotta A, Tirrell M . Wormlike micelle formation in peptide-lipid conjugates driven by secondary structure transformation of the headgroups. J Phys Chem B. 2009; 113(42):13711-4. DOI: 10.1021/jp901727q. View

Wang Y, de Kruijff R, Lovrak M, Guo X, Eelkema R, van Esch J . Access to Metastable Gel States Using Seeded Self-Assembly of Low-Molecular-Weight Gelators. Angew Chem Int Ed Engl. 2018; 58(12):3800-3803. DOI: 10.1002/anie.201812412. View

Cheng Y, Sun C, Liu R, Yang J, Dai J, Zhai T . A Multifunctional Peptide-Conjugated AIEgen for Efficient and Sequential Targeted Gene Delivery into the Nucleus. Angew Chem Int Ed Engl. 2019; 58(15):5049-5053. DOI: 10.1002/anie.201901527. View

Nakase I, Niwa M, Takeuchi T, Sonomura K, Kawabata N, Koike Y . Cellular uptake of arginine-rich peptides: roles for macropinocytosis and actin rearrangement. Mol Ther. 2004; 10(6):1011-22. DOI: 10.1016/j.ymthe.2004.08.010. View

10.

Reichow S, Hamma T, Ferre-DAmare A, Varani G . The structure and function of small nucleolar ribonucleoproteins. Nucleic Acids Res. 2007; 35(5):1452-64. PMC: 1865073. DOI: 10.1093/nar/gkl1172. View

11.

Whitmore L, Wallace B . DICHROWEB, an online server for protein secondary structure analyses from circular dichroism spectroscopic data. Nucleic Acids Res. 2004; 32(Web Server issue):W668-73. PMC: 441509. DOI: 10.1093/nar/gkh371. View

12.

Zhan J, Cai Y, Ji S, He S, Cao Y, Ding D . Spatiotemporal Control of Supramolecular Self-Assembly and Function. ACS Appl Mater Interfaces. 2017; 9(11):10012-10018. DOI: 10.1021/acsami.7b00784. View

13.

OSullivan J, Pai D, Cridge A, Engelke D, Ganley A . The nucleolus: a raft adrift in the nuclear sea or the keystone in nuclear structure?. Biomol Concepts. 2014; 4(3):277-86. PMC: 5100006. DOI: 10.1515/bmc-2012-0043. View

14.

Hein N, Hannan K, George A, Sanij E, Hannan R . The nucleolus: an emerging target for cancer therapy. Trends Mol Med. 2013; 19(11):643-54. DOI: 10.1016/j.molmed.2013.07.005. View

15.

Zhang C, Shafi R, Lampel A, MacPherson D, Pappas C, Narang V . Switchable Hydrolase Based on Reversible Formation of Supramolecular Catalytic Site Using a Self-Assembling Peptide. Angew Chem Int Ed Engl. 2017; 56(46):14511-14515. DOI: 10.1002/anie.201708036. View

16.

Quin J, Devlin J, Cameron D, Hannan K, Pearson R, Hannan R . Targeting the nucleolus for cancer intervention. Biochim Biophys Acta. 2014; 1842(6):802-16. DOI: 10.1016/j.bbadis.2013.12.009. View

17.

Kato M, McKnight S . A Solid-State Conceptualization of Information Transfer from Gene to Message to Protein. Annu Rev Biochem. 2017; 87:351-390. DOI: 10.1146/annurev-biochem-061516-044700. View

18.

Gao Y, Shi J, Yuan D, Xu B . Imaging enzyme-triggered self-assembly of small molecules inside live cells. Nat Commun. 2012; 3:1033. PMC: 3521559. DOI: 10.1038/ncomms2040. View

19.

Medina S, Schneider J . Cancer cell surface induced peptide folding allows intracellular translocation of drug. J Control Release. 2015; 209:317-26. PMC: 4458427. DOI: 10.1016/j.jconrel.2015.05.267. View

20.

Zhang Y, Kuang Y, Gao Y, Xu B . Versatile small-molecule motifs for self-assembly in water and the formation of biofunctional supramolecular hydrogels. Langmuir. 2010; 27(2):529-37. PMC: 3019246. DOI: 10.1021/la1020324. View