H. pylori - Ace Infectious
Drug Development Targeting the HtrA of H. pylori
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Drug Development Targeting the HtrA of H. pylori

Ace Infectious provides drug development services targeting the pathogenic mechanism of H. pylori. High-temperature requirement A (HtrA) is an important periplasmic protein of H. pylori that destroys the layer of gastric epithelial cells. We provide drug development services targeting HtrA to help develop drugs that protect the gastric epithelial cell layer.

HtrA

HtrA can cause severe damage to the gastric epithelium. HtrA facilitates the entry of H. pylori into intracellular spaces by cleaving the extracellular matrix protein fibronectin, cell adhesion molecule E-cadherin, and tight junction protein-8 of the gastric epithelium through proteolytic activity. In addition, HtrA is essential for the survival of H. pylori. Among these H. pylori strains, only the N6 strain has been found to delete htrA or mutate the htrA. HtrA has chaperone activity that is important for protein quality control of H. pylori. Zarzecka's study has shown that HtrA is also important for H. pylori stress responses in stressful environments. In summary, HtrA is an ideal H. pylori therapeutic target.

Services for HtrA's drug development

Ace Infectious's HtrA-based drug development services take full account of the structure and function of HtrA and we offer drug development services for HtrA from three directions.

The overall structure of the full-length H. pylori HtrA monomerFig. 1 The overall structure of the full-length H. pylori HtrA monomer (Zhang et al., 2019).

Drug development services for HtrA by blocking its entry into the periplasm

Based on that H. pylori HrtA requires the Sec translocon to enter the periplasm, we offer drug development services targeting this translocate mechanism. We provide small molecule drug development services targeting the translocation-related signal peptide of HtrA, and we also provide small molecule drug development services targeting Sec translocon molecules, such as SecA.

Drug development services for HtrA by disrupting the assembly of HtrA

Firstly, we provide drug development services targeting the amino-terminal cleavage sites of HtrA to disrupt the auto-cleavage of HtrA which affects the hydrolase activity of HtrA. Then, we provide drug development services targeting the N-terminal domain (NT) of HtrA to disrupt the protease activity of HtrA through structural disruption. In addition, we provide drug development services targeting the PDZ1 domain of HtrA to disrupt the growth of H. pylori under stressful conditions.

Drug development services targeting the active site of HtrA

As the hydrolysis of E-cadherin by HtrA is the prerequisite for linking T4SS and integrin β1, which helps to inject CagA into gastric cells, we provide small molecule drug development services targeting the protease active site of HtrA. Then, we also provide to develop substrate-derived peptide inhibitors based on the [VITA]-[VITA]-x-x-D-[DN] sequence of E-cadherin which is the preferential cleavage site.

Contact us

Ace Infectious provides drug development services targeting the HtrA of H. pylori to help develop drugs that mitigate the damage caused by H. pylori to the gastric epithelial cell layer. We provide drug development services from the translocation of HtrA, assembly of HtrA, and active sites of HtrA. Please contact us for professional HtrA drug development services.

References

  1. Tegtmeyer, N.; et al. Characterisation of worldwide Helicobacter pylori strains reveals genetic conservation and essentiality of serine protease HtrA. Molecular microbiology. 2016, 99(5): 925-44
  2. Zhang, Z.; et al. The unique trimeric assembly of the virulence factor HtrA from Helicobacter pylori occurs via N-terminal domain swapping. Journal of Biological Chemistry. 2019, 294(20): 7990-8000.
  3. Zarzecka, U.; et al. Chaperone activity of serine protease HtrA of Helicobacter pylori as a crucial survival factor under stress conditions. Cell Communication and Signaling. 2019, 17(1): 161.

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