Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Sep;98(3):305-322.
doi: 10.1111/cbdd.13899. Epub 2021 Jun 27.

Discovery of novel antibacterial agents: Recent developments in D-alanyl-D-alanine ligase inhibitors

Yinhui Qin  1 , Linlin Xu  2 , Yuetai Teng  3 , Yinhu Wang  4 , Peizhi Ma  1
Affiliations
Review

Discovery of novel antibacterial agents: Recent developments in D-alanyl-D-alanine ligase inhibitors

Yinhui Qin et al. Chem Biol Drug Des. 2021 Sep.

Abstract

Bacterial infections can cause serious problems that threaten public health over a long period of time. Moreover, the continuous emergence of drug-resistant bacteria necessitates the development of novel antibacterial agents. D-alanyl-D-alanine ligase (Ddl) is an indispensable adenosine triphosphate-dependent bacterial enzyme involved in the biosynthesis of peptidoglycan precursor, which catalyzes the ligation of two D-alanine molecules into one D-alanyl-D-alanine dipeptide. This dipeptide is an essential component of the intracellular peptidoglycan precursor, uridine diphospho-N-acetylmuramic acid (UDP-MurNAc)-pentapeptide, that maintains the integrity of the bacterial cell wall by cross-linking the peptidoglycan chain, and is crucial for the survival of pathogens. Consequently, Ddl is expected to be a promising target for the development of antibacterial agents. In this review, we present a brief introduction regarding the structure and function of Ddl, as well as an overview of the various Ddl inhibitors currently being used as antibacterial agents, specifically highlighting their inhibitory activities, structure-activity relationships and mechanisms of action.

Keywords: Ddl; antibacterial agents; biological activity; inhibitors; peptidoglycan; structure-activity relationships.

PubMed Disclaimer

References

REFERENCES

    1. Albar, O. A. M., Oconnor, C. D., Giles, I. G., & Akhtar, M. (1992). D-alanine: D-alanine ligase of Escherichia coli. Expression, purification and inhibitory studies on the cloned enzyme. Biochemical Journal, 282, 747-752. https://doi.org/10.1042/bj2820747
    1. Ameryckx, A., Pochet, L., Wang, G., Yildiz, E., Saadi, B. E., Wouters, J., Van Bambeke, F., & Frédérick, R. (2020). Pharmacomodulations of the benzoyl-thiosemicarbazide scaffold reveal antimicrobial agents targeting D-alanyl-D-alanine ligase in bacterio. European Journal of Medicinal Chemistry, 200, 13. https://doi.org/10.1016/j.ejmech.2020.112444
    1. Ameryckx, A., Thabault, L., Pochet, L., Leimanis, S., Poupaert, J. H., Wouters, J., & Frederick, R. (2018). 1-(2-Hydroxybenzoy1)-thiosemicarbazides are promising antimicrobial agents targeting D-alanine-D-alanine ligase in bacterio. European Journal of Medicinal Chemistry, 159, 324-338. https://doi.org/10.1016/j.ejmech.2018.09.067
    1. Azam, S. S., Abbasi, S. W., Akhtar, A. S., & Mirza, M. L. (2014). Comparative modeling and molecular docking studies of D-Alanine:D-alanine ligase: A target of antibacterial drugs. Medicinal Chemistry Research, 23(9), 4108-4137. https://doi.org/10.1007/s00044-014-0970-8
    1. Barreteau, H., Kovac, A., Boniface, A., Sova, M., Gobec, S., & Blanot, D. (2008). Cytoplasmic steps of peptidoglycan biosynthesis. FEMS Microbiology Reviews, 32(2), 168-207. https://doi.org/10.1111/j.1574-6976.2008.00104.x

Publication types

MeSH terms

LinkOut - more resources