Insights into the mechanism of action of two analogues of aurein 2.2

Biochimica Et Biophysica Acta. Biomembranes
Nigare RaheemSuzana K Straus

Abstract

The naturally occurring host defense peptide (HDP), aurein 2.2, secreted by the amphibian Litoria aurea, acts as a moderate antibacterial, affecting Gram positive bacteria such as Staphylococcus aureus by forming selective ion pores. In a quest to find more active analogues of aurein 2.2, peptides 73 and 77 were discovered. These peptides were rich in arginine and tryptophan and found to have MICs of 4 μg/mL. Here we examined what impact the increased charge from +2 to +3 and a slight increase in hydrophobic moment relative to aurein 2.2 had on the mechanism of action of these two analogues. Using a time-kill assay, both peptides 73 and 77 were found to kill bacteria more effectively than the parent peptide. Using solution CD and NMR, the peptides were found to not adopt a continuous α-helical structure, i.e. the analogues were not helical from residue 1-13 like the parent peptide. Results obtained from oriented CD (OCD), DiSC35 and pyranine assays and a gel retardation experiment showed that the peptides did not function by membrane perturbation and further showed that peptide 73 and 77 did not interact with DNA. Overall, the data were consistent with these peptides acting as cell penetrating peptides with intracellular target...Continue Reading

References

Jan 6, 1981·Biochemistry·S W Provencher, J Glöckner
Jun 1, 1995·Trends in Biotechnology·D Barra, M Simmaco
Oct 1, 1993·Progress in Neurobiology·L H Lazarus, M Attila
Feb 27, 1999·Protein Science : a Publication of the Protein Society·N SreeramaR W Woody
Jun 1, 1996·Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases·R. E. W. Hancock, T. J. Falla
Mar 28, 2002·Journal of the American Chemical Society·Zhengshuang ShiNeville R Kallenbach
Feb 4, 2003·Proceedings of the National Academy of Sciences of the United States of America·Antoine KichlerBurkhard Bechinger
Jun 20, 2003·Nature Reviews. Drug Discovery·Brian L Bray
Mar 29, 2005·The Lancet Infectious Diseases·Robert Ew Hancock
Apr 28, 2005·Antimicrobial Agents and Chemotherapy·Dawn M E BowdishRobert E W Hancock
Jun 8, 2006·Biochimica Et Biophysica Acta·David I ChanHans J Vogel
Jul 19, 2006·Clinical Microbiology Reviews·Håvard JenssenRobert E W Hancock
Sep 26, 2006·Nucleic Acids Research·Christophe MarchandYves Pommier
Dec 13, 2006·Nature Biotechnology·Robert E W Hancock, Hans-Georg Sahl
Jul 2, 2008·Infection and Immunity·Joerg OverhageRobert E W Hancock
Nov 11, 2008·Plasmid·Rebecca M Corrigan, Timothy J Foster
Aug 4, 2009·Methods in Molecular Biology·Dirk F H WinklerRobert E W Hancock
Dec 19, 2009·European Biophysics Journal : EBJ·Andrea Holt, J Antoinette Killian
Jan 26, 2010·Journal of Controlled Release : Official Journal of the Controlled Release Society·El-Sayed KhafagyKozo Takayama
Jan 28, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Masae SugawaraBurkhard Bechinger
Aug 23, 2012·Frontiers in Immunology·Hannah UlmHans-Georg Sahl
Oct 25, 2012·Physical Chemistry Chemical Physics : PCCP·David I FernandezFrances Separovic
Mar 12, 2013·Trends in Microbiology·Thaddeus B Stanton
Mar 20, 2013·Biochimica Et Biophysica Acta·David I FernandezFrances Separovic
Apr 5, 2013·Biopolymers·Evan F Haney, Robert E W Hancock
Apr 9, 2013·Biochimica Et Biophysica Acta·Evan F HaneyHans J Vogel
Apr 8, 2014·Proceedings of the National Academy of Sciences of the United States of America·Michaela WenzelJulia Elisabeth Bandow
May 24, 2014·PLoS Pathogens·César de la Fuente-NúñezRobert E W Hancock

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Citations

Aug 17, 2020·International Journal of Molecular Sciences·Surajit Bhattacharjya, Suzana K Straus
Jul 9, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Matthew DraytonSuzana K Straus
Dec 24, 2020·International Journal of Molecular Sciences·Taylor Rounds, Suzana K Straus
Apr 2, 2021·Biochimica Et Biophysica Acta. Biomembranes·Dror E WarschawskiIsabelle Marcotte

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