Cell-Penetrating Peptides and Transportan

Overview

Journal Pharmaceutics

Publisher MDPI

Date 2021 Jul 2

PMID 34210007

Citations 19

Authors

Ulo Langel

Affiliations

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Abstract

In the most recent 25-30 years, multiple novel mechanisms and applications of cell-penetrating peptides (CPP) have been demonstrated, leading to novel drug delivery systems. In this review, I present a brief introduction to the CPP area with selected recent achievements. This is followed by a nostalgic journey into the research in my own laboratories, which lead to multiple CPPs, starting from transportan and paving a way to CPP-based therapeutic developments in the delivery of bio-functional materials, such as peptides, proteins, vaccines, oligonucleotides and small molecules, etc.

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References

Tsang O, Wong J . Proteogenomic interrogation of cancer cell lines: an overview of the field. Expert Rev Proteomics. 2021; 18(3):221-232. DOI: 10.1080/14789450.2021.1914594. View

Console S, Marty C, Garcia-Echeverria C, Schwendener R, Ballmer-Hofer K . Antennapedia and HIV transactivator of transcription (TAT) "protein transduction domains" promote endocytosis of high molecular weight cargo upon binding to cell surface glycosaminoglycans. J Biol Chem. 2003; 278(37):35109-14. DOI: 10.1074/jbc.M301726200. View

McKeown A, Naro J, Huskins L, Almeida P . A thermodynamic approach to the mechanism of cell-penetrating peptides in model membranes. Biochemistry. 2010; 50(5):654-62. PMC: 3035854. DOI: 10.1021/bi1013358. View

Kurrikoff K, Freimann K, Veiman K, Peets E, Piirsoo A, Langel U . Effective lung-targeted RNAi in mice with peptide-based delivery of nucleic acid. Sci Rep. 2019; 9(1):19926. PMC: 6934651. DOI: 10.1038/s41598-019-56455-2. View

Cosme P, Ye J, Sears S, Wojcikiewicz E, Terentis A . Label-Free Confocal Raman Mapping of Transportan in Melanoma Cells. Mol Pharm. 2018; 15(3):851-860. DOI: 10.1021/acs.molpharmaceut.7b00601. View

Langel U, Pooga M, Kairane C, Zilmer M, Bartfai T . A galanin-mastoparan chimeric peptide activates the Na+,K(+)-ATPase and reverses its inhibition by ouabain. Regul Pept. 1996; 62(1):47-52. DOI: 10.1016/0167-0115(96)00002-x. View

Vasconcelos L, Lehto T, Madani F, Radoi V, Hallbrink M, Vukojevic V . Simultaneous membrane interaction of amphipathic peptide monomers, self-aggregates and cargo complexes detected by fluorescence correlation spectroscopy. Biochim Biophys Acta Biomembr. 2017; 1860(2):491-504. DOI: 10.1016/j.bbamem.2017.09.024. View

Barany-Wallje E, Andersson A, Graslund A, Maler L . NMR solution structure and position of transportan in neutral phospholipid bicelles. FEBS Lett. 2004; 567(2-3):265-9. DOI: 10.1016/j.febslet.2004.04.079. View

Regberg J, Srimanee A, Erlandsson M, Sillard R, Dobchev D, Karelson M . Rational design of a series of novel amphipathic cell-penetrating peptides. Int J Pharm. 2014; 464(1-2):111-6. DOI: 10.1016/j.ijpharm.2014.01.018. View

10.

van den Berg A, Dowdy S . Protein transduction domain delivery of therapeutic macromolecules. Curr Opin Biotechnol. 2011; 22(6):888-93. DOI: 10.1016/j.copbio.2011.03.008. View

11.

Zhang W, Song J, Zhang B, Liu L, Wang K, Wang R . Design of acid-activated cell penetrating peptide for delivery of active molecules into cancer cells. Bioconjug Chem. 2011; 22(7):1410-5. DOI: 10.1021/bc200138d. View

12.

Carreras-Badosa G, Maslovskaja J, Periyasamy K, Urgard E, Padari K, Vaher H . NickFect type of cell-penetrating peptides present enhanced efficiency for microRNA-146a delivery into dendritic cells and during skin inflammation. Biomaterials. 2020; 262:120316. DOI: 10.1016/j.biomaterials.2020.120316. View

13.

Pooga M, Land T, Bartfai T, Langel U . PNA oligomers as tools for specific modulation of gene expression. Biomol Eng. 2001; 17(6):183-92. DOI: 10.1016/s1389-0344(01)00075-2. View

14.

Pari E, Horvati K, Bosze S, Biri-Kovacs B, Szeder B, Zsila F . Drug Conjugation Induced Modulation of Structural and Membrane Interaction Features of Cationic Cell-Permeable Peptides. Int J Mol Sci. 2020; 21(6). PMC: 7139830. DOI: 10.3390/ijms21062197. View

15.

Veiman K, Kunnapuu K, Lehto T, Kiisholts K, Parn K, Langel U . PEG shielded MMP sensitive CPPs for efficient and tumor specific gene delivery in vivo. J Control Release. 2015; 209:238-47. DOI: 10.1016/j.jconrel.2015.04.038. View

16.

Muratovska A, Eccles M . Conjugate for efficient delivery of short interfering RNA (siRNA) into mammalian cells. FEBS Lett. 2004; 558(1-3):63-8. DOI: 10.1016/S0014-5793(03)01505-9. View

17.

Freimann K, Arukuusk P, Kurrikoff K, Vasconcelos L, Veiman K, Uusna J . Optimization of in vivo DNA delivery with NickFect peptide vectors. J Control Release. 2016; 241:135-143. DOI: 10.1016/j.jconrel.2016.09.022. View

18.

Buss C, Bhatia S . Nanoparticle delivery of immunostimulatory oligonucleotides enhances response to checkpoint inhibitor therapeutics. Proc Natl Acad Sci U S A. 2020; 117(24):13428-13436. PMC: 7306768. DOI: 10.1073/pnas.2001569117. View

19.

Nielsen P, Egholm M, Berg R, Buchardt O . Sequence-selective recognition of DNA by strand displacement with a thymine-substituted polyamide. Science. 1991; 254(5037):1497-500. DOI: 10.1126/science.1962210. View

20.

Ptaszynska N, Gucwa K, Olkiewicz K, Heldt M, Serocki M, Stupak A . Conjugates of Ciprofloxacin and Levofloxacin with Cell-Penetrating Peptide Exhibit Antifungal Activity and Mammalian Cytotoxicity. Int J Mol Sci. 2020; 21(13). PMC: 7369900. DOI: 10.3390/ijms21134696. View