Linker chemistry and connectivity fine-tune the immune response and kinetic solubility of conjugated NOD2/TLR7 agonists

Janež, Špela (avtor), Guzelj, Samo (avtor), Jakopin, Žiga (avtor)

There is a growing interest in developing novel immune potentiators capable of eliciting a cellular immune response. We tackle this challenge by harnessing the synergistic cross-activation between two innate immune receptors─the nucleotide-binding oligomerization domain-containing protein 2 (NOD2) and Toll-like receptor 7 (TLR7). Herein, we investigate the structure–activity relationship of a series of novel conjugated NOD2/TLR7 agonists incorporating a variety of flexible aliphatic, poly(ethylene glycol)-based and triazole-featuring linkers. Our findings reveal potent immune-enhancing properties of conjugates in human primary peripheral blood mononuclear cells, characterized by a Th1/Th17 polarized cytokine response. Importantly, we demonstrate that both the chemistry of the linker and the site of linkage affect the immune fingerprint and the kinetic solubility of these conjugated agonists. These results shed further light on the immunostimulatory potential of NOD2/TLR7 cross-activation and provide insights for designing innovative immune potentiators.

• Jezik: Angleški jezik
• Ključne besede: agonists, amines, conjugate acid-base pairs, peptides, proteins, solubility
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FFA - Fakulteta za farmacijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2024
• Št. strani: Str. 1723–1731
• Številčenje: Vol. 35, iss. 11
• PID: 20.500.12556/RUL-165195
• UDK: 615.4:54:616.097
• ISSN pri članku: 1520-4812
• DOI: 10.1021/acs.bioconjchem.4c00321
• COBISS.SI-ID: 211169539
• Datum objave v RUL: 26.11.2024

Gradivo je del revije

• Naslov: Bioconjugate chemistry
• Skrajšan naslov: Bioconjug. chem.
• Založnik: American Chemical Society
• ISSN: 1520-4812
• COBISS.SI-ID: 3419674

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: agonisti, amini, konjugirani kislinsko-bazični pari, peptidi, proteini, topnost, imunski odziv, farmacevtska kemija