H. pylori adhesins are important for the colonization of H. pylori. Ace Therapeutics provides drug development services targeting H. pylori adhesins to help develop H. pylori therapeutics from the perspective of reducing colonization. Since H. pylori have multiple adhesins and the ligands of some adhesins need to be further explored, we currently provide drug development services targeting important adhesins as described below. Of course, if you have a need for drug development targeting other H. pylori adhesins, please let us know!
Fig. 1 Graphical representation of H. pylori adhesin interactions with host cell proteins (Bonsor & Sundberg, 2019).
Drug development targeting BabA
BabA (HopS) is in the Hop family and can bind to ABO group antigens Leb, A-Leb, and B-Leb. Most notably, BabA shows reversible pH sensitivity and can selectively bind to the gastric mucosa according to the acidic environment of the stomach. This means that BabA is an important protein for H. pylori's long-term adaptation to the gastric acid environment.
Ace Therapeutics offers drug development services targeting BabA. We take full consideration of BabA as an adhesin that binds H. pylori to ABO blood group antigen-glycosylated gastric mucosa with the pH-regulated binding mechanism. We provide services to search and design suitable drugs targeting BabA's pH-sensor site (residue 199 of the crowning helical loop). Then, we offer small molecule drug development targeting loop 1 (the connecting strands loop) to reduce BabA binding to A-Leb and B-Leb, and we offer disulfide development services for loop 2 (the crowning helical loop) to reduce BabA binding to glycans.
Drug development targeting SabA
SabA (HopP) can bind to sialylated glycans (such as s-Lex), Neu5Acα3-neolactohexaosylceramide, Neu5Acα3-neolactooctaosylceramide, and glycoproteins that are sialylated (such as MUC7 and laminin). H. pylori infection activates IL-8 in host cells, thus promoting increased synthesis of s-Lex. This promotes further H. pylori adhesion in the inflamed gastric mucosal tissue leading to long-term colonization by H. pylori.
Ace Therapeutics offers drug development services targeting SabA. We provide small molecule drug development and ligand analog development services targeting the potential ligand-binding pocket on the SabA surface. Then, we provide drug development services targeting the Gln-159 of SabA to inhibit the binding to s-Lex and Lex.
Drug development services targeting HopQ
Although HopQ was found outside of cagPAI, it is required for CagA translocation. We provide peptide structural analog development services based on the N-terminal dimerization domain of CEACAM-1, -3, -5, and -6 to aid in the development of competitive inhibitors that reduce adhesion. In addition, we provide drug development services targeting the adhesion-related region β-hairpin insertion, which is in the 3+4 helix bundle domain of HopQ.
Contact us
Ace Therapeutics provides drug development services targeting adhesins, such as BabA, SabA, and HopQ. We also provide drug development services targeting the adhesin CagL, which is described in the drug development services targeting the cag pathogenicity island. If you need to develop drugs targeting other H. pylori adhesins, such as OpiA, HomB, and HorB, please contact us for consultation.
References
- Bonsor, D. A.; Sundberg, E. J. Roles of adhesion to epithelial cells in gastric colonization by Helicobacter pylori. Helicobacter pylori in Human Diseases. 2019: 57-75.
- Bugaytsova, J. A.; et al. Helicobacter pylori adapts to chronic infection and gastric disease via pH-responsive BabA-mediated adherence. Cell Host & Microbe. 2017, 21(3): 376-89.
- Javaheri, A.; et al. Helicobacter pylori adhesin HopQ engages in a virulence-enhancing interaction with human CEACAMs. Nature Microbiology. 2016, 2(1): 16189.
※ All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
