Projects

1)    Development of cellular transporters

Cell-penetrating peptides, CPP, are able to function as cellular transporters through biological membranes. As these CPP:s or transportans, can carry another agent, e.g. a protein, they offer additional methods for research and therapeutic use. However, the mechanisms behind such cellular delivery remain obscured and are worth of detailed studies. Currently, our interest is also concerned with the possibility to deliver drugs across blood brain barrier. Cellular delivery of peptides, short oligonucleotides such as siRNA, peptide nucleic acid oligomers, proteins and even plasmids for transfection has been achieved.


2)    Studies and mimicry of protein-protein interactions

In recent years, the modeling of protein-protein interactions for development of potential drugs has become of great interest for us. We have concentrated on understanding of these interactions at the level of 7TM receptors - G-proteins and transcription factors in case of disorders where the signal transduction seems to be of crucial importance. The disorders connected to the cellular signal transduction system which are of interest for us are diabetes (NIDDM), Alzheimer's disease and cancer. Delivery of the drugs across blood brain barrier and selective targeting is also of interest using the transport peptides and even here the first results are very promising and we are continuing these studies.

 

Selected Publications

1. Langel,Ü. (2015) Preface. Methods in Molecular Biology, 1324, v-viii.

2. Pooga,M., and Langel,Ü. (2015) Classes of cell-penetrating peptides. Methods in Molecular Biology, 1324, 3-28.

3. Cerrato,C.P., Künnapuu,K., and Langel,Ü. (2017) Cell-penetrating peptides with intracellular organelle targeting, Exp.Opinion Drug Del., 14(2), 245-255.

4. Cerrato,C.P., and Langel,Ü. (2017) Effect of a Fusion Peptide by Covalent Conjugation of a Mitochondrial Cell-Penetrating Peptide and a Glutathione Analog Peptide. Molecular Therapy: Methods & Clinical Development, 5, 221-231.

5. Dowaidar,M., Regberg,J., Dobchev,D.A., Lehto,T., Hällbrink,M., Karelson,M., and Langel,Ü. (2017) Refinement of a quantitative structure-activity relationship model for prediction of cell-penetrating peptide based transfection systems. Int.J.Pept.Res.Therap., 23, 91-100.

6. Dowaidar,M., Gestin,M., Cerrato,C.P., Jafferali,M.H., Margus,H., Kivistik,P.A., Ezzat,K., Hallberg,E., Pooga,M., Hällbrink.,M., and Langel,Ü. (2017) Role of autophagy in cell-penetrating peptide transfection model. Scientific Reports. 7(1), 12635, 1-14, DOI:10.1038/s41598-017-12747-z.

7. Dowaidar,M., Gestin,M., and Langel,Ü. (2017) Cell penetrating peptide uptake mechanisms. In :  “Peptides and Peptide-based Biomaterials and their Biomedical Applications”, Springer book series “Advances in Experimental Medicine and Biology”. In press.

8. Dowaidar,M., Abdelhamid,H.N., Hällbrink,M., Zou,X., and Langel,Ü. (2017) Magnetic nanoparticles Assisted Self-assembly of Cell Penetrating Peptides-Oligonucleotides complexes for gene Delivery. Scientific Reports, 7(1):9159, 1-11.

9. Dowaidar,M., Abdelhamid,H.N., Hällbrink,M., Zou,X., and Langel,Ü. (2017) Graphene oxide nanosheets in complex with cell penetrating peptides for oligonucleotides delivery. Biochim. Biophys. Acta - General Subjects, 1861, 2334-2341.

 

Books  

Ü. Langel, B. Cravatt, A. Gräslund, G. von Heijne, T.Land, S.Niessen, and M.Zorko (2010) Introduction to peptides and proteins, CRC Press, Taylor and Francis Group, Boca Raton, London, New York, ISBN : 978-1-4200-6412-4.

Langel, Ü., Ed. (2011) Cell-Penetrating Peptides. Methods and Protocols. Methods in Molecular Biology, Humana Press., vol. 683, ISBN: 978-1-60761-918-5.