Amino Acid Composition Determines Peptide Activity Spectrum and Hot-Spot-Based Design of Merecidin

Advanced Biosystems
Xiuqing WangGuangshun Wang

Abstract

There is a great interest in developing the only human cathelicidin into therapeutic molecules. The major antimicrobial region of human LL-37 corresponds to residues 17-32. The resultant peptide GF-17 shows a broad spectrum of antimicrobial activity against both Gram-positive and negative bacteria. By reducing the hydrophobic content, we previously succeeded in converting the broad-spectrum GF-17 to two narrow-spectrum peptides (GF-17d3 and KR-12) with activity against Gram-negative bacteria. This study demonstrates that substitution of multiple basic amino acids by hydrophobic alanines makes a broad-spectrum peptide 17BIPHE2 (designed based on GF-17d3) active against Staphylococcal pathogens but not other bacteria tested. Taken together, our results reveal distinct charge and hydrophobic requirements for peptides to kill Gram-positive or Gram-negative bacteria. This finding is in line with the bioinformatics analysis of the peptides in the Antimicrobial Peptide Database (http://aps.unmc.edu/AP). In addition, a hot spot arginine is identified and used to design merecidin with reduced toxicity to human cells. Merecidin protects wax moth larvae (Galleria mellonella) from the infection of methicillin-resistant S. aureus USA300. Th...Continue Reading

References

Mar 6, 1998·Trends in Biotechnology·R E Hancock, R Lehrer
Sep 16, 1998·Antimicrobial Agents and Chemotherapy·J TurnerR I Lehrer
Dec 11, 1999·Biochimica Et Biophysica Acta·R M Epand, H J Vogel
Jan 25, 2002·Nature·Michael Zasloff
Jul 2, 2008·Infection and Immunity·Joerg OverhageRobert E W Hancock
Jul 2, 2008·Antimicrobial Agents and Chemotherapy·Guangshun WangRobert W Buckheit
Oct 17, 2008·The Biochemical Journal·Francesca MorgeraAlessandro Tossi
Dec 17, 2008·Current Opinion in Hematology·Anastasia Nijnik, Robert E W Hancock
Mar 20, 2009·Journal of Medicinal Chemistry·Christopher D FjellArtem Cherkasov
Jul 8, 2009·Antimicrobial Agents and Chemotherapy·Raquel F EpandRichard M Epand
Nov 16, 2011·Antimicrobial Agents and Chemotherapy·Guangshun WangRichard M Epand
Feb 23, 2012·The Journal of Dermatology·Shin Morizane, Richard L Gallo
Jul 19, 2012·Journal of the American Chemical Society·Biswajit Mishra, Guangshun Wang
Jul 11, 2013·Frontiers in Immunology·Allen J Duplantier, Monique L van Hoek
Dec 17, 2014·Proceedings of the National Academy of Sciences of the United States of America·Mahmoud H Abou AlaiwaMichael J Welsh
Jan 6, 2015·Methods in Molecular Biology·Guangshun Wang
Mar 26, 2015·Pharmaceuticals·Guangshun WangXiuqing Wang
Nov 26, 2015·Nucleic Acids Research·Guangshun WangZhe Wang
Jan 29, 2016·ACS Medicinal Chemistry Letters·Biswajit MishraGuangshun Wang
Jan 13, 2018·Science Translational Medicine·Anna de BreijPeter H Nibbering

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Citations

Oct 4, 2020·Journal of Computer-aided Molecular Design·Hossein AghazadehKamran Pooshang Bagheri
Dec 10, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Hanqi WeiYingxia Zhang
Mar 18, 2020·Computational and Structural Biotechnology Journal·Jesus A BeltranCarlos A Brizuela
Apr 24, 2021·ACS Infectious Diseases·Jayaram Lakshmaiah NarayanaGuangshun Wang
Jun 3, 2021·Antibiotics·Kylen E Ridyard, Joerg Overhage
Aug 8, 2021·International Journal of Molecular Sciences·Isabella Hernández-Aristizábal, Iván Darío Ocampo-Ibáñez

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