Recent advances in chemical protein synthesis: method developments and biological applications

Science China Chemistry, Journal Year: 2024, Volume and Issue: 67(4), P. 1060 - 1096

Published: March 12, 2024

Language: Английский

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Multifunctional Lipidated Protein Carrier with a Built-In Adjuvant as a Universal Vaccine Platform Potently Elevates Immunogenicity of Weak Antigens

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(8), P. 6822 - 6838

Published: April 8, 2024

Weak antigens represented by MUC1 are poorly immunogenic, which greatly constrains the development of relevant vaccines. Herein, we developed a multifunctional lipidated protein as carrier, in TLR1/2 agonist Pam3CSK4 was conjugated to N-terminus MUC1-loaded carrier BSA through pyridoxal 5′-phosphate-mediated transamination reaction. The resulting Pam3CSK4–BSA-MUC1 conjugate subsequently incorporated into liposomes, biomimics membrane structure tumor cells. results indicated that this significantly enhanced antigen uptake APCs and obviously augmented retention vaccine at injection site. Compared with BSA-MUC1 + groups, evoked 22- 11-fold increases MUC1-specific IgG titers. Importantly, elicited robust cellular immunity inhibited growth. This is first time constructed enhance immunogenicity, universal platform exhibits promise for utilization various vaccines, holding potential further clinical application.

Language: Английский

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Conjugation of TLR7 and TLR7/8 agonists onto weak protein antigen via versatile oxime ligation for enhanced vaccine efficacy

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 278, P. 134620 - 134620

Published: Aug. 9, 2024

Language: Английский

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Poly(I:C)/c-GAMP/Alum ternary adjuvant system synergistically enhances the immunogenicity of glycopeptide antigen

Journal of Carbohydrate Chemistry, Journal Year: 2023, Volume and Issue: 42(7-9), P. 252 - 267

Published: Nov. 22, 2023

The highly glycosylated mucin 1 (MUC1) serves as a promising target for cancer vaccines. However, the weak immunogenicity of MUC1 greatly impedes its application. Here, we covalently linked glycopeptide to carrier protein bovine serum albumin (BSA), and resulting BSA-MUC1 conjugate was integrated with ternary adjuvant system comprising TLR3 agonist poly(I:C), STING c-GAMP, Alum adjuvant. Compared adjuvant-free Alum-adjuvanted groups, group induced 18.3- 10.9-fold increases in MUC1-specific IgG titers, effectively suppressed tumor growth. These findings may propose straightforward yet effective strategy designing vaccines, offering prospects treatment.

Language: Английский

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Role of NLRP3 Inflammasome in Nanoparticle Adjuvant-Mediated Immune Response

Biomaterials Science, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

The nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) inflammasome is pivotal in orchestrating the immune response induced by nanoparticle adjuvants. Understanding intricate mechanisms underlying activation of NLRP3 these adjuvants crucial for deciphering their immunomodulatory properties. This review explores involvement mediating responses triggered It delves into signaling pathways and cellular involved activation, highlighting its significance modulating efficacy safety nanoparticle-based A comprehensive grasp interplay between holds promise optimizing vaccine design advancing immunotherapeutic strategies.

Language: Английский

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Diphtheria Toxoid-Derived T-Helper Epitope and α-galactosylceramide Synergistically Enhance the Immunogenicity of Glycopeptide Antigen

ACS Pharmacology & Translational Science, Journal Year: 2024, Volume and Issue: 7(12), P. 3889 - 3901

Published: Nov. 4, 2024

The tumor-associated antigen MUC1 is an attractive target for immunotherapy, however, its weak immunogenicity limits the induction of antitumor immune responses. To overcome this limitation, in study, glycopeptide was covalently linked with a diphtheria toxin-derived T-helper epitope (DT331–345). Subsequently, resulting DT-MUC1 physically mixed natural killer T cell agonist αGalCer to explore their immunomodulatory synergy. Biological results demonstrated that compared MUC1+αGalCer and groups, specific IgG antibody titer DT-MUC1+αGalCer group increased by 189- 3-fold, respectively, indicating synergistically enhanced αGalCer. Moreover, vaccine induced potent cellular responses significantly inhibited growth B16-MUC1 tumors vivo. Furthermore, it found anti-MUC1 equivalent palmitoylated (P1-DT-MUC1+αGalCer) higher than doubly (P2-DT-MUC1+αGalCer), suggesting easily synthesized may not require lipid chain modification already possess good amphiphilicity. This first time helper enhance immunogenicity, study provide effective design strategy MUC1-targeted vaccines offer novel insights into fully synthetic peptide vaccines.

Language: Английский

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Periodate activation via metals and metal-based complexes: progress in degradation properties and mechanisms

Water Science & Technology, Journal Year: 2024, Volume and Issue: 90(5), P. 1681 - 1705

Published: Aug. 23, 2024

ABSTRACT Residuals of refractory organics in water create a deep hazard to the environment and human health, hence it is urgent develop efficient approaches remove organics. Being novel oxidizer, periodate (PI, IO4-) considered be stable advanced oxidation processes for degrading organics, such as antibiotics, dyes, pesticides, etc. Since activity PI alone low, necessary activate form active species effectively removing The studies activation via monometallic, bimetallic, metal oxides, complexes, etc., have obtained more concerns owing high efficiency decomposing However, no reviews related these been published recent years. This review summarized properties uses PI, analyzed degradation mechanisms various metals metal-based complexes activating highlighted limitations well future research directions.

Language: Английский

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Synergistic Immune Augmentation Enabled by Covalently Conjugating TLR4 and NOD2 Agonists

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 278, P. 116792 - 116792

Published: Aug. 26, 2024

Language: Английский

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