Cholic Acid-Based Antimicrobial Peptide Mimics as Antibacterial Agents.
- Publisher:
- MDPI AG
- Publication Type:
- Journal Article
- Citation:
- International Journal of Molecular Sciences, 2022, 23, (9), pp. 1-24
- Issue Date:
- 2022-04-21
Open Access
Copyright Clearance Process
- Recently Added
- In Progress
- Open Access
This item is open access.
Full metadata record
Field | Value | Language |
---|---|---|
dc.contributor.author | Wu, J | |
dc.contributor.author | Yu, TT | |
dc.contributor.author | Kuppusamy, R | |
dc.contributor.author | Hassan, MM | |
dc.contributor.author |
Alghalayini, A https://orcid.org/0000-0002-2308-0256 |
|
dc.contributor.author | Cranfield, CG | |
dc.contributor.author | Willcox, MDP | |
dc.contributor.author | Black, DS | |
dc.contributor.author | Kumar, N | |
dc.date.accessioned | 2022-12-13T02:25:41Z | |
dc.date.available | 2022-04-16 | |
dc.date.available | 2022-12-13T02:25:41Z | |
dc.date.issued | 2022-04-21 | |
dc.identifier.citation | International Journal of Molecular Sciences, 2022, 23, (9), pp. 1-24 | |
dc.identifier.issn | 1422-0067 | |
dc.identifier.issn | 1661-6596 | |
dc.identifier.uri | http://hdl.handle.net/10453/164342 | |
dc.description.abstract | There is a significant and urgent need for the development of novel antibacterial agents to tackle the increasing incidence of antibiotic resistance. Cholic acid-based small molecular antimicrobial peptide mimics are reported as potential new leads to treat bacterial infection. Here, we describe the design, synthesis and biological evaluation of cholic acid-based small molecular antimicrobial peptide mimics. The synthesis of cholic acid analogues involves the attachment of a hydrophobic moiety at the carboxyl terminal of the cholic acid scaffold, followed by the installation of one to three amino acid residues on the hydroxyl groups present on the cholic acid scaffold. Structure-activity relationship studies suggest that the tryptophan moiety is important for high antibacterial activity. Moreover, a minimum of +2 charge is also important for antimicrobial activity. In particular, analogues containing lysine-like residues showed the highest antibacterial potency against Gram-positive S. aureus. All di-substituted analogues possess high antimicrobial activity against both Gram-positive S. aureus as well as Gram-negative E. coli and P. aeruginosa. Analogues 17c and 17d with a combination of these features were found to be the most potent in this study. These compounds were able to depolarise the bacterial membrane, suggesting that they are potential antimicrobial pore forming agents. | |
dc.format | Electronic | |
dc.language | eng | |
dc.publisher | MDPI AG | |
dc.relation.ispartof | International Journal of Molecular Sciences | |
dc.relation.isbasedon | 10.3390/ijms23094623 | |
dc.rights | info:eu-repo/semantics/openAccess | |
dc.subject | 0399 Other Chemical Sciences, 0604 Genetics, 0699 Other Biological Sciences | |
dc.subject.classification | Chemical Physics | |
dc.subject.mesh | Anti-Bacterial Agents | |
dc.subject.mesh | Anti-Infective Agents | |
dc.subject.mesh | Antimicrobial Peptides | |
dc.subject.mesh | Cholic Acid | |
dc.subject.mesh | Escherichia coli | |
dc.subject.mesh | Microbial Sensitivity Tests | |
dc.subject.mesh | Staphylococcus aureus | |
dc.subject.mesh | Structure-Activity Relationship | |
dc.subject.mesh | Anti-Bacterial Agents | |
dc.subject.mesh | Anti-Infective Agents | |
dc.subject.mesh | Antimicrobial Peptides | |
dc.subject.mesh | Cholic Acid | |
dc.subject.mesh | Escherichia coli | |
dc.subject.mesh | Microbial Sensitivity Tests | |
dc.subject.mesh | Staphylococcus aureus | |
dc.subject.mesh | Structure-Activity Relationship | |
dc.subject.mesh | Escherichia coli | |
dc.subject.mesh | Staphylococcus aureus | |
dc.subject.mesh | Cholic Acid | |
dc.subject.mesh | Anti-Infective Agents | |
dc.subject.mesh | Anti-Bacterial Agents | |
dc.subject.mesh | Microbial Sensitivity Tests | |
dc.subject.mesh | Structure-Activity Relationship | |
dc.subject.mesh | Antimicrobial Peptides | |
dc.title | Cholic Acid-Based Antimicrobial Peptide Mimics as Antibacterial Agents. | |
dc.type | Journal Article | |
utslib.citation.volume | 23 | |
utslib.location.activity | Switzerland | |
utslib.for | 0399 Other Chemical Sciences | |
utslib.for | 0604 Genetics | |
utslib.for | 0699 Other Biological Sciences | |
pubs.organisational-group | /University of Technology Sydney | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Science | |
pubs.organisational-group | /University of Technology Sydney/Strength - CHT - Health Technologies | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Science/School of Life Sciences | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Science/School of Mathematical and Physical Sciences | |
pubs.organisational-group | /University of Technology Sydney/Strength - IBMD - Initiative for Biomedical Devices | |
pubs.organisational-group | /University of Technology Sydney/Centre for Health Technologies (CHT) | |
utslib.copyright.status | open_access | * |
pubs.consider-herdc | false | |
dc.date.updated | 2022-12-13T02:25:35Z | |
pubs.issue | 9 | |
pubs.publication-status | Published | |
pubs.volume | 23 | |
utslib.citation.issue | 9 |
Abstract:
There is a significant and urgent need for the development of novel antibacterial agents to tackle the increasing incidence of antibiotic resistance. Cholic acid-based small molecular antimicrobial peptide mimics are reported as potential new leads to treat bacterial infection. Here, we describe the design, synthesis and biological evaluation of cholic acid-based small molecular antimicrobial peptide mimics. The synthesis of cholic acid analogues involves the attachment of a hydrophobic moiety at the carboxyl terminal of the cholic acid scaffold, followed by the installation of one to three amino acid residues on the hydroxyl groups present on the cholic acid scaffold. Structure-activity relationship studies suggest that the tryptophan moiety is important for high antibacterial activity. Moreover, a minimum of +2 charge is also important for antimicrobial activity. In particular, analogues containing lysine-like residues showed the highest antibacterial potency against Gram-positive S. aureus. All di-substituted analogues possess high antimicrobial activity against both Gram-positive S. aureus as well as Gram-negative E. coli and P. aeruginosa. Analogues 17c and 17d with a combination of these features were found to be the most potent in this study. These compounds were able to depolarise the bacterial membrane, suggesting that they are potential antimicrobial pore forming agents.
Please use this identifier to cite or link to this item:
Download statistics for the last 12 months
Not enough data to produce graph