Three dimensions illustrate the need to optimize H. pylori therapeutic peptides and proteins (TPPs). To begin, proteins are initially digested in the stomach, and most are structurally destroyed by gastric acid and pepsin. Therefore, optimizing H. pylori TPPs that work in the stomach is essential to adapt to the gastric environment. Then, for natural peptides or proteins that are expressed at a low level in the original species or are difficult to extract, it is necessary to optimize such H. pylori TPPs to adapt to other expression systems. Finally, peptides or proteins obtained from natural products may not be effective enough in treating H. pylori infection, and such possible H. pylori TPPs need to be optimized to improve the therapeutic effect.
Ace Infectious provides three optimization strategies to meet the above needs. Further, we also provide other related optimizations. Below is a detailed description of H. pylori optimization services for H. pylori TPPs.
Fig. 1 Optimization of H. pylori TPPs.
For optimizing the stability of H. pylori TPPs, we offer a variety of solutions such as amino acid substitution, cyclization, N-cap modifications, C-terminal modifications, splicing, polyethylene glycol (PEG) chemical modifications, and peptide stapling. In addition, we have conducted in-depth studies on the optimization of reducing the degradation of pepsin and also on the structures of acid-stable proteins such as pepsin, human cathelicidin LL-37, and midkine. All of these allow us to easily achieve rapid optimization of stability enhancement of H. pylori TPPs.
Optimization to adapt to other expression systems
Ace Infectious has several established protein expression systems, and we have conducted in-depth research on bacterial, fungal, plant, animal, and viral protein expression systems. We can select suitable expression systems for TPPs and optimize the expression of the codons used for expression.
Optimization to improve targeting capability
We offer three main approaches to improve the targetability of TPPs against H. pylori. First, we offer to appropriately add partial signal peptide sequences of therapeutic target proteins for TPPs to improve the chances of collision between TPPs and therapeutic targets. Second, we offer to add the molecular part of bacteriophage binding to H. pylori for TPPs to increase the frequency of protein-based drug binding to H. pylori. Third, we offer optimization modifications such as amino acid substitutions, amino acid modifications, glycosylation, and peptide stapling to increase the affinity of TPPs to targets.
pH-response activation optimization
Based on the fact that TPPs against H. pylori work in an acidic environment, we provide pH-responsive activation optimization to allow TPPs to form active forms in the appropriate environment. We primarily utilize the property of glutamate protonation in an acidic environment, and in addition, we utilize the properties of histidine, isoleucine, and phenylalanine in an acidic environment.
Optimization to enhance the disruption of H. pylori cell membranes
Drugs targeting microbial cell membranes are thought to be difficult to develop resistance to. And most antimicrobial peptides can physically disrupt bacterial cell membranes, resulting in cell membrane porosity. Therefore, we provide optimization for TPPs to enhance the disruption of H. pylori cell membranes. For example, we provide the addition of cationic poly (α-amino acids) or we provide α-helical peptide stapling for TPPs.
Ace Infectious is thoughtful and experienced in the optimization of H. pylori TPPs. We offer five optimization services to help the development of H. pylori TPPs. If you have any of the above optimization needs, please contact us for customized optimization services.
- Choudhury, A.; et al. In vitro inhibition of H. pylori in a preferential manner using bioengineered L. lactis releasing guided Antimicrobial peptides. bioRxiv. 2021, 06: 448109.
- Shen, W.; et al. From antimicrobial peptides to antimicrobial poly(α-amino acid)s. Advanced Healthcare Materials. 2018, 7(20): 1800354.
※ All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.