H. pylori - Ace Infectious
Drug Development Targeting the pH Homeostasis Mechanism of H. pylori
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Drug Development Targeting the pH Homeostasis Mechanism of H. pylori

For diseases caused by microorganisms, the most basic treatment is to start from the survival mechanism of the microorganism. The faster the microorganism is killed, the fewer drug-resistant microorganisms will be produced and the less harm will be done.

Ace Infectious provides drug development services targeting the survival mechanisms of H. pylori to help treat H. pylori infection. Based on the fact that H. pylori must adapt to extreme gastric acid environments, we provide drug development services targeting the pH homeostasis mechanism of H. pylori. We mainly provide drug development services targeting urease, carbonic anhydrase, and acid-activated urea channel (Urel) of H. pylori.

Enzymes associated with H. pylori acid homeostasis.Fig. 1 Enzymes associated with H. pylori acid homeostasis.

Development of drugs targeting urease of H. pylori

H. pylori can adapt to the extremely acidic environment of the human stomach, and one of its important enzymes is urease. Although urease is also a virulence factor for H. pylori, it is more important for the survival of H. pylori as the urease-negative H. pylori mutant is unable to colonize the stomach of sterile piglets.

Ace Infectious offers drug development services for urease-related targets. We offer services to develop urease inhibitors based on structural information of H. pylori urease to directly reduce the activity of H. pylori urease. Based on the nickel-dependent properties of urease, we also offer drug development services targeting nickel-responsive regulator (NikR) to effect urease expression.

Development of drugs targeting carbonic anhydrase of H. pylori

Another enzyme that enables H. pylori to adapt to the stomach's acidic environment is carbonic anhydrase. Carbonic anhydrase is the enzyme that works in conjunction with urease to perform acid homeostasis. The cooperation between the two enzymes is shown in Fig. 2. H. pylori carbonic anhydrase balances CO2, HCO3- and H+ concentration.

The cooperation between carbonic anhydrase and urease.Fig. 2 The cooperation between carbonic anhydrase and urease.

Ace Infectious provides drug development services for α-carbonic anhydrase which is in the periplasm and β-carbonic anhydrase which is in the cytoplasm. We offer to develop analogues of sulfonamides as they inhibit carbonic anhydrase and have bactericidal activity against H. pylori. Then, we provide metal complexation inhibitor development for the zinc-binding core of β-carbonic anhydrase. We also provide peptide and protein drug development for periplasmic α-carbonic anhydrase.

Development of drugs targeting Urel of H. pylori

Urease decomposes urea to produce neutralizing ammonia. We provide drug development services targeting the Urel, which affects urea permeability. We offer small-molecule inhibitor development and peptide inhibitor development for this channel to affect H. pylori pH homeostasis by blocking urea transport.

Contact us

H. pylori can't survive if it can't adapt to the gastric acid environment. Ace Infectious provides drug development services targeting the H. pylori pH homeostasis mechanism. Currently, we offer drug development services for urease, carbonic anhydrase, and Urel of H. pylori, and you can contact us if you have other needs.

References

  1. Campestre, C.; et al. Carbonic anhydrases: New perspectives on protein functional role and inhibition in Helicobacter pylori. Frontiers in Microbiology. 2021, 12: 629163.
  2. Liu, Q.; et al. Arylamino containing hydroxamic acids as potent urease inhibitors for the treatment of Helicobacter pylori infection. European Journal of Medicinal Chemistry. 2018, 156: 126-36.
  3. Modak, J. K.; et al. Anti-Helicobacter pylori activity of ethoxzolamide. Journal of Enzyme Inhibition and Medicinal Chemistry. 2019, 34(1): 1660-67.

※ All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.