Cell adhesion inhibiting peptides exhibit potent anticancer activity and modulate intestinal microbiota

Chen, Yu-Fon; Yeh, Yao‐Tsung; Su, Yu‐Chu; Liao, Chorng-An; Huang, Cheng-Hsieh; Cheng, Ying-Jung; Jan, Jeng‐Shiung

doi:10.1016/j.matdes.2022.111303

Cited by 4 publications

(1 citation statement)

References 51 publications

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“…FAs are protein complexes attaching cells to the ECM cytoskeleton, providing actin–integrin links [ 44 ]. Anticancer peptides affect cell-adhesion molecules (CAMs) to prevent tumor metastasis [ 45 ]. The KEGG pathway analysis shows that the anticancer adjuvant targets glioma ( Supplementary Materials S4 ), which is achievable because the ACP candidate is predicted to pass the BBB.…”

Section: Resultsmentioning

confidence: 99%

Immunomodulatory Peptides as Vaccine Adjuvants and Antimicrobial Agents

Hemmati,

Saeidikia,

Seradj

et al. 2024

Pharmaceuticals

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The underdevelopment of adjuvant discovery and diversity, compared to core vaccine technology, is evident. On the other hand, antibiotic resistance is on the list of the top ten threats to global health. Immunomodulatory peptides that target a pathogen and modulate the immune system simultaneously are promising for the development of preventive and therapeutic molecules. Since investigating innate immunity in insects has led to prominent achievements in human immunology, such as toll-like receptor (TLR) discovery, we used the capacity of the immunomodulatory peptides of arthropods with concomitant antimicrobial or antitumor activity. An SVM-based machine learning classifier identified short immunomodulatory sequences encrypted in 643 antimicrobial peptides from 55 foe-to-friend arthropods. The critical features involved in efficacy and safety were calculated. Finally, 76 safe immunomodulators were identified. Then, molecular docking and simulation studies defined the target of the most optimal peptide ligands among all human cell-surface TLRs. SPalf2-453 from a crab is a cell-penetrating immunoadjuvant with antiviral properties. The peptide interacts with the TLR1/2 heterodimer. SBsib-711 from a blackfly is a TLR4/MD2 ligand used as a cancer vaccine immunoadjuvant. In addition, SBsib-711 binds CD47 and PD-L1 on tumor cells, which is applicable in cancer immunotherapy as a checkpoint inhibitor. MRh4-679 from a shrimp is a broad-spectrum or universal immunoadjuvant with a putative Th1/Th2-balanced response. We also implemented a pathway enrichment analysis to define fingerprints or immunological signatures for further in vitro and in vivo immunogenicity and reactogenicity measurements. Conclusively, combinatorial machine learning, molecular docking, and simulation studies, as well as systems biology, open a new opportunity for the discovery and development of multifunctional prophylactic and therapeutic lead peptides.

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Section: Resultsmentioning

confidence: 99%

Immunomodulatory Peptides as Vaccine Adjuvants and Antimicrobial Agents

Hemmati,

Saeidikia,

Seradj

et al. 2024

Pharmaceuticals

View full text Add to dashboard Cite

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Peptide‐Based Nanoparticles Suppress Hepatic Inflammation via Blockage of Human Antigen R

Chen,

Wang,

Jan

2024

Small

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Human antigen R (HuR), which is a mRNA‐binding protein that stabilizes and regulates mRNA translation, is found to have increased expression in inflammation, cancer and other diseases, making HuR to be a promising drug target. This study reports a peptide‐based nanoparticle (NP) system exhibits potent anti‐inflammatory activity to ameliorate acute liver injury via the ability of peptides to inhibit the mRNA binding site of HuR and block downstream signaling. Molecular modeling provided structural evidence indicating that the peptides interact with the RNA‐binding site of HuR, mainly via hydrogen‐bonding and hydrophobic interactions. These peptide‐based NPs can act as nanocarriers to deliver peptides into cells to compete with the mRNA binding site of HuR, evidenced by the reduction of antibody recognition to the native protein and the exhibition of anti‐inflammatory activity against activated macrophage cells, with no adverse effect in vitro and in vivo. In LPS/D‐GalN‐induced hepatic sepsis with high dosage of LPS/GalN, administration of the NPs significantly attenuated necrosis and HuR expression, resulting in the significant improvement of animal survival rate, suggesting their therapeutic potential for hepatic inflammation and a broad range of HuR‐overexpressed diseases.

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