Chemically modified and conjugated antimicrobial peptides against superbugs

Antimicrobial resistance (AMR) is one of the greatest threats to human health that, by 2050, will lead to more deaths from bacterial infections than cancer. New antimicrobial agents, both broad-spectrum and selective, that do not induce AMR are urgently required. Antimicrobial peptides (AMPs) are a...

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Published inChemical Society reviews Vol. 5; no. 8; pp. 4932 - 4973
Main Authors Li, Wenyi, Separovic, Frances, O'Brien-Simpson, Neil M, Wade, John D
Format Journal Article
LanguageEnglish
Published England Royal Society of Chemistry 26.04.2021
Subjects
antibiotic resistance
Antibiotics
Antimicrobial agents
antimicrobial peptides
antimicrobial properties
glycosylation
human health
Peptides
therapeutics
Online AccessGet full text
ISSN0306-0012
1460-4744
1460-4744
DOI10.1039/d0cs01026j

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Abstract Antimicrobial resistance (AMR) is one of the greatest threats to human health that, by 2050, will lead to more deaths from bacterial infections than cancer. New antimicrobial agents, both broad-spectrum and selective, that do not induce AMR are urgently required. Antimicrobial peptides (AMPs) are a novel class of alternatives that possess potent activity against a wide range of Gram-negative and positive bacteria with little or no capacity to induce AMR. This has stimulated substantial chemical development of novel peptide-based antibiotics possessing improved therapeutic index. This review summarises recent synthetic efforts and their impact on analogue design as well as their various applications in AMP development. It includes modifications that have been reported to enhance antimicrobial activity including lipidation, glycosylation and multimerization through to the broad application of novel bio-orthogonal chemistry, as well as perspectives on the direction of future research. The subject area is primarily the development of next-generation antimicrobial agents through selective, rational chemical modification of AMPs. The review further serves as a guide toward the most promising directions in this field to stimulate broad scientific attention, and will lead to new, effective and selective solutions for the several biomedical challenges to which antimicrobial peptidomimetics are being applied. Chemical modification of antimicrobial peptides augments their antibacterial action via multiple mechanisms.
AbstractList Antimicrobial resistance (AMR) is one of the greatest threats to human health that, by 2050, will lead to more deaths from bacterial infections than cancer. New antimicrobial agents, both broad-spectrum and selective, that do not induce AMR are urgently required. Antimicrobial peptides (AMPs) are a novel class of alternatives that possess potent activity against a wide range of Gram-negative and positive bacteria with little or no capacity to induce AMR. This has stimulated substantial chemical development of novel peptide-based antibiotics possessing improved therapeutic index. This review summarises recent synthetic efforts and their impact on analogue design as well as their various applications in AMP development. It includes modifications that have been reported to enhance antimicrobial activity including lipidation, glycosylation and multimerization through to the broad application of novel bio-orthogonal chemistry, as well as perspectives on the direction of future research. The subject area is primarily the development of next-generation antimicrobial agents through selective, rational chemical modification of AMPs. The review further serves as a guide toward the most promising directions in this field to stimulate broad scientific attention, and will lead to new, effective and selective solutions for the several biomedical challenges to which antimicrobial peptidomimetics are being applied.Antimicrobial resistance (AMR) is one of the greatest threats to human health that, by 2050, will lead to more deaths from bacterial infections than cancer. New antimicrobial agents, both broad-spectrum and selective, that do not induce AMR are urgently required. Antimicrobial peptides (AMPs) are a novel class of alternatives that possess potent activity against a wide range of Gram-negative and positive bacteria with little or no capacity to induce AMR. This has stimulated substantial chemical development of novel peptide-based antibiotics possessing improved therapeutic index. This review summarises recent synthetic efforts and their impact on analogue design as well as their various applications in AMP development. It includes modifications that have been reported to enhance antimicrobial activity including lipidation, glycosylation and multimerization through to the broad application of novel bio-orthogonal chemistry, as well as perspectives on the direction of future research. The subject area is primarily the development of next-generation antimicrobial agents through selective, rational chemical modification of AMPs. The review further serves as a guide toward the most promising directions in this field to stimulate broad scientific attention, and will lead to new, effective and selective solutions for the several biomedical challenges to which antimicrobial peptidomimetics are being applied.
Antimicrobial resistance (AMR) is one of the greatest threats to human health that, by 2050, will lead to more deaths from bacterial infections than cancer. New antimicrobial agents, both broad-spectrum and selective, that do not induce AMR are urgently required. Antimicrobial peptides (AMPs) are a novel class of alternatives that possess potent activity against a wide range of Gram-negative and positive bacteria with little or no capacity to induce AMR. This has stimulated substantial chemical development of novel peptide-based antibiotics possessing improved therapeutic index. This review summarises recent synthetic efforts and their impact on analogue design as well as their various applications in AMP development. It includes modifications that have been reported to enhance antimicrobial activity including lipidation, glycosylation and multimerization through to the broad application of novel bio-orthogonal chemistry, as well as perspectives on the direction of future research. The subject area is primarily the development of next-generation antimicrobial agents through selective, rational chemical modification of AMPs. The review further serves as a guide toward the most promising directions in this field to stimulate broad scientific attention, and will lead to new, effective and selective solutions for the several biomedical challenges to which antimicrobial peptidomimetics are being applied.
Antimicrobial resistance (AMR) is one of the greatest threats to human health that, by 2050, will lead to more deaths from bacterial infections than cancer. New antimicrobial agents, both broad-spectrum and selective, that do not induce AMR are urgently required. Antimicrobial peptides (AMPs) are a novel class of alternatives that possess potent activity against a wide range of Gram-negative and positive bacteria with little or no capacity to induce AMR. This has stimulated substantial chemical development of novel peptide-based antibiotics possessing improved therapeutic index. This review summarises recent synthetic efforts and their impact on analogue design as well as their various applications in AMP development. It includes modifications that have been reported to enhance antimicrobial activity including lipidation, glycosylation and multimerization through to the broad application of novel bio-orthogonal chemistry, as well as perspectives on the direction of future research. The subject area is primarily the development of next-generation antimicrobial agents through selective, rational chemical modification of AMPs. The review further serves as a guide toward the most promising directions in this field to stimulate broad scientific attention, and will lead to new, effective and selective solutions for the several biomedical challenges to which antimicrobial peptidomimetics are being applied. Chemical modification of antimicrobial peptides augments their antibacterial action via multiple mechanisms.
Author Separovic, Frances
Wade, John D
Li, Wenyi
O'Brien-Simpson, Neil M
AuthorAffiliation University of Melbourne
Melbourne Dental School
The Florey Institute of Neuroscience and Mental Health
Centre for Oral Health Research
Bio21 Institute
School of Chemistry
AuthorAffiliation_xml – name: Melbourne Dental School
– name: Bio21 Institute
– name: The Florey Institute of Neuroscience and Mental Health
– name: Centre for Oral Health Research
– name: University of Melbourne
– name: School of Chemistry
Author_xml – sequence: 1
  givenname: Wenyi
  surname: Li
  fullname: Li, Wenyi
– sequence: 2
  givenname: Frances
  surname: Separovic
  fullname: Separovic, Frances
– sequence: 3
  givenname: Neil M
  surname: O'Brien-Simpson
  fullname: O'Brien-Simpson, Neil M
– sequence: 4
  givenname: John D
  surname: Wade
  fullname: Wade, John D
BackLink https://www.ncbi.nlm.nih.gov/pubmed/33710195$$D View this record in MEDLINE/PubMed
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Notes Frances Separovic is a biophysical chemist and deputy director of the Bio21 Institute, University of Melbourne. Frances joined the University in 1996, where she became the first woman professor of chemistry (2005). She has developed solid-state NMR techniques to determine the structure and dynamics of molecules in biological membranes with a focus on membrane-active peptides. Frances is a Fellow of the Biophysical Society, an ISMAR Fellow and was the first female chemist elected to the Australian Academy of Science (2012). She is an IUPAC Distinguished Woman of Chemistry and was appointed an Officer of the Order of Australia in 2019.
Neil O'Brien-Simpson is a Professor, appointed 2018, at The University of Melbourne. After working with ICI Chemicals and Polymers then graduating from Edinburgh Napier University, he completed his PhD in Australia on peptide polymer vaccines in 1997. His research focuses on chemical biology, combining microbiology, peptide/organic chemistry and immunology to address major scientific questions in the application of antimicrobial peptides/materials, nanoparticles for peptide and vaccine delivery targeting bacteria, cancer and bacterial outer membrane vesicles-host interactions. He received the Alan Docking Science Award (2017), is an author of more than 120 papers, 15 patents and has mentored 21 PhD students.
John D. Wade obtained his PhD in 1980 at Monash University, Australia. He received a Nuffield Foundation Fellowship to Cambridge, UK, at the MRC Laboratory of Molecular Biology working with R. C. Sheppard. Since 1983, he has been at the now Florey Institute of Neuroscience and Mental Health, University of Melbourne, where he heads the Laboratory of Peptide and Protein Chemistry. His interests are in chemical peptide synthesis of complex, functionalized peptides including antimicrobial peptides. Professor Wade is an NHMRC of Australia Principal Research Fellow and a Fellow of both the Royal Australian Chemical Institute and the Royal Society of Chemistry.
Wenyi Li obtained his doctoral degree from The University of Melbourne in 2016 working with Professors John Wade and Frances Separovic. His thesis on antimicrobial peptide development won the Graham Johnston Best Thesis Award from the RACI and the University of Melbourne's Monica Reum Memorial Prize. He then worked with Professor Christian Hackenberger at the Leibniz Institute of Molecular Pharmacology, Germany, as a Leibniz-DAAD postdoctoral fellow working on protein semisynthesis and chemical ligation. In 2018, he returned to The University of Melbourne to work on antibacterial polymers and peptides in the groups of Professors Neil O'Brien-Simpson and Greg Qiao.
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Snippet Antimicrobial resistance (AMR) is one of the greatest threats to human health that, by 2050, will lead to more deaths from bacterial infections than cancer....
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SubjectTerms antibiotic resistance
Antibiotics
Antimicrobial agents
antimicrobial peptides
antimicrobial properties
glycosylation
human health
Peptides
therapeutics
Title Chemically modified and conjugated antimicrobial peptides against superbugs
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