Skip to main page content
U.S. flag

An official website of the United States government

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 May 24;29(11):2492.
doi: 10.3390/molecules29112492.

Recent Advances in Amphipathic Peptidomimetics as Antimicrobial Agents to Combat Drug Resistance

Ma Su  1 , Yongxiang Su  2
Affiliations
Review

Recent Advances in Amphipathic Peptidomimetics as Antimicrobial Agents to Combat Drug Resistance

Ma Su et al. Molecules. .

Abstract

The development of antimicrobial drugs with novel structures and clear mechanisms of action that are active against drug-resistant bacteria has become an urgent need of safeguarding human health due to the rise of bacterial drug resistance. The discovery of AMPs and the development of amphipathic peptidomimetics have lay the foundation for novel antimicrobial agents to combat drug resistance due to their overall strong antimicrobial activities and unique membrane-active mechanisms. To break the limitation of AMPs, researchers have invested in great endeavors through various approaches in the past years. This review summarized the recent advances including the development of antibacterial small molecule peptidomimetics and peptide-mimic cationic oligomers/polymers, as well as mechanism-of-action studies. As this exciting interdisciplinary field is continuously expanding and growing, we hope this review will benefit researchers in the rational design of novel antimicrobial peptidomimetics in the future.

Keywords: antimicrobial agents; drug resistance; peptidomimetics.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Summary of antimicrobial amphipathic peptidomimetics in this review.
Scheme 1
Scheme 1
Chemical structures of acid-based ceragenin derivatives.
Scheme 2
Scheme 2
Chemical structures of PMX-30063.
Scheme 3
Scheme 3
Chemical structures of oligopeptide derivatives.
Scheme 4
Scheme 4
Chemical structures of small molecule guanidine derivatives.
Scheme 5
Scheme 5
Chemical structures of xanthone-based small molecules.
Scheme 6
Scheme 6
Chemical structures of other small molecule peptidomimetics.
Scheme 7
Scheme 7
Chemical structures of β-peptide derivative polymers.
Scheme 8
Scheme 8
Chemical structures of poly(2-oxazoline).
Scheme 9
Scheme 9
Chemical structures of polycarbonates.
Scheme 10
Scheme 10
Chemical structures of polysulfoniums.
Scheme 11
Scheme 11
Chemical structures of polyisocyanate copolymers.
Figure 2
Figure 2
Proposed models of antibacterial mechanisms of AMPs.
Figure 3
Figure 3
(a) The carpet/detergent-like model of the antimicrobial peptide pepD2M. (b) The membrane-thinning model and the pore-forming model of melittin [116]. (Adapted with permission from Nature Communications 2023, 14, 5464. Copyright 2023 Springer Nature).
Scheme 12
Scheme 12
Chemical structures of FDA-approved natural AMPs.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Mancuso G., Midiri A., Gerace E., Biondo C. Bacterial antibiotic resistance: The most critical pathogens. Pathogens. 2021;10:1310. doi: 10.3390/pathogens10101310. - DOI - PMC - PubMed
    1. Saiman L. Infectious diseases of the fetus and newborn infant. JAMA. 2012;307:1865–1866. doi: 10.1001/jama.307.17.1865. - DOI
    1. McKenney J., Bauman S., Neary B., Detels R., French A., Margolick J. Prevalence, correlates, and outcomes of cryptococcal antigen positivity among patients with AIDS, United States, 1986–2012. Clin. Infect. Dis. 2015;60:959–965. doi: 10.1093/cid/ciu937. - DOI - PMC - PubMed
    1. Bee G.C.W., Lokken-Toyli K.L., Yeung S.T., Rodriguez L., Zangari T., Anderson E.E., Ghosh S., Rothlin C.V., Brodin P., Khanna K.M., et al. Age-dependent differences in efferocytosis determine the outcome of opsonophagocytic protection from invasive pathogens. Immunity. 2023;56:1255–1268. doi: 10.1016/j.immuni.2023.03.018. - DOI - PMC - PubMed
    1. Darby E.M., Trampari E., Siasat P., Gaya M.S., Alav I., Webber M.A., Blair J.M.A. Molecular mechanisms of antibiotic resistance revisited. Nat. Rev. Microbiol. 2023;21:280–295. doi: 10.1038/s41579-022-00820-y. - DOI - PubMed

MeSH terms