Rational design of peptides active against the gram positive bacteria Staphylococcus aureus

Proteins
C LandonF Vovelle

Abstract

In an attempt to increase the antimicrobial activity of the insect defensin from Anopheles gambiae, which is active against Staphylococcus aureus at low concentration, hybrid defensins were designed by combining conserved sequence regions and variable regions of insect defensins. Their activity against S. aureus strains sensitive and resistant to conventional antibiotics was evaluated, and the toxicity of the most active molecules was tested. The three-dimensional structure of Anopheles gambiae defensin and five hybrids were determined by NMR and molecular modelling. This strategy led to the design of two chimeric defensins with increased activity compared with the native molecule, but one of them appears to be toxic to mice at a rather low concentration. The structure of the CS alphabeta motif, which is a characteristic of insect defensin, is sensitive to sequence modifications, in particular in the N-terminal loop. The existence of the CS alphabeta is most probably a prerequisite for the stability and the activity of the molecule, but is not sufficient by itself since the hybrid displaying the best defined structure is not active against the tested strains. The analysis of the structure, in relation with the activity and the ...Continue Reading

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Citations

May 16, 2012·Proceedings of the National Academy of Sciences of the United States of America·Shunyi ZhuDavid J Craik
Mar 27, 2012·PloS One·Christian W Gruber, Markus Muttenthaler
Jan 16, 2014·Molecular Biology and Evolution·Shunyi ZhuJan Tytgat
Dec 2, 2014·Biochimica Et Biophysica Acta·Wonyoung Lee, Dong Gun Lee
Sep 15, 2012·Biochemical and Biophysical Research Communications·Bin Gao, Shunyi Zhu
May 24, 2012·Developmental and Comparative Immunology·Zhenting Zhang, Shunyi Zhu
May 2, 2015·Peptides·Renata de Oliveira Dias, Octavio Luiz Franco
Jul 21, 2009·Biochemical and Biophysical Research Communications·Bin GaoShunyi Zhu
Nov 18, 2008·Biochimica Et Biophysica Acta·Lanlan YuThorsten Wohland
Apr 21, 2019·Medicinal Research Reviews·Thanh-Nhat PhamPascal Sonnet
Apr 17, 2016·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jiajia WuShunyi Zhu
Jan 29, 2016·Biologie aujourd'hui·Max GoyffonGrazyna Faure
Jul 28, 2017·Frontiers in Chemistry·Johannes Koehbach
Nov 16, 2013·ACS Chemical Biology·Bin Gao, Shunyi Zhu

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