H. pylori - Ace Infectious
Drug Development Targeting the Self-protection Mechanism of H. pylori
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Drug Development Targeting the Self-protection Mechanism of H. pylori

The antioxidant system and cell wall of H. pylori play an important protective role for H. pylori. Disruption of its antioxidant system and cell wall synthesis-related enzymes can effectively inhibit the growth of H. pylori. Ace Infectious offers drug development services targeting enzymes related to H. pylori's self-protection mechanism to help develop therapeutics by disrupting the survival of H. pylori. And we offer drug development services targeting thioredoxin C (TrxC), UDP-3-O-[(R)-3-hydroxymyristoyl]-N-acetyl glucosamine deacetylase (LpxC), and transglycosylase.

Drug development targeting H. pylori self-protection mechanism - Ace InfectiousFig. 1 Drug development targeting H. pylori self-protection mechanism - Ace Infectious.

Drug development targeting the thioredoxin (Trx) system of H. pylori

Reactive oxygen species (ROS) can damage biological macromolecules (DNA, lipids, and proteins), which can cause great damage to the structure of the organism. H. pylori lacks the glutathione-glutaredoxin (GSH) reduction system compared to normal bacteria and relies only on the Trx reduction system to resist oxidative stress. Ace Infectious provides drug development services for enzymes of the Trx system, including TrxR, TrxA, and TrxC, to disrupt the Trx reduction system of H. pylori. We offer to develop structural analogs of ebselen [2-phenyl-1,2 benzisoselenazol-3(2H)-one] to inhibit the enzymatic activity of TrxR and Trx. In addition, we also offer to develop auranofin analogs to inhibit thioredoxin reductase activity by binding to thiol and selenol groups on the enzyme.

Drug development targeting LpxC of H. pylori

The outer membrane of H. pylori acts as a permeability barrier that protects H. pylori from many antibiotics. We can assist in the treatment of H. pylori infections by disrupting the outer membrane structure of H. pylori. Lipopolysaccharide (LPS) is the main component of the outer membrane. Therefore, Ace Infectious provides drug development services targeting LPS-related enzymes. Among them, LpxC is an important enzyme for lipid-A biosynthesis. And we provide drug development services targeting its Zn2+-dependent characteristic and its affinity for hydrophobic substrates.

Drug development targeting transglycosylase of H. pylori

Another important enzyme associated with H. pylori cell wall synthesis is transglycosylase. Therefore, we also offer drug development services targeting transglycosylase which is important for the synthesis of peptidoglycan of H. pylori, and for the maintenance of the spiral form of H. pylori. Based on previous studies that moenomycin A inhibits clinically resistant H. pylori strains by inhibiting the transglycosylase enzyme, we also offer drug development based on moenomycin A.

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To develop H. pylori therapeutic drugs from various aspects, Ace Infectious provides drug development services targeting the self-protection mechanism. We help develop drugs that disrupt the antioxidant system of H. pylori to kill H. pylori by damaging the structure of H. pylori through the massive accumulation of ROS. And, we help develop drugs that disrupt the cell wall structure of H. pylori to facilitate the action of gastric acid and other drugs on H. pylori. If you have a need for drug development targeting the self-protection mechanism of H. pylori, please contact us for professional services.

References

  1. Kuhns Lisa, G.; et al. Comparative roles of the two Helicobacter pylori thioredoxins in preventing macromolecule damage. Infection and Immunity. 2015, 83(7): 2935-43.
  2. Pasala, C.; et al. Hierarchical-clustering, scaffold-mining exercises and dynamics simulations for effectual inhibitors against lipid-a biosynthesis of Helicobacter pylori. Cellular and Molecular Bioengineering. 2019, 12(3): 255-74.
  3. Chen, X.; et al. Targeting the bacterial transglycosylase: Antibiotic development from a structural perspective. ACS Infectious Diseases. 2019, 5(9): 1493-504.

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