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Synthesis and immunostimulatory activity of sugar-conjugated TLR7 ligands.

Abstract：

:Toll-like receptors (TLRs) are a type of pattern recognition receptors (PRRs), which are activated by recognizing pathogen-associated molecular patterns (PAMPs). The activation of TLRs initiates innate immune responses and subsequently leads to adaptive immune responses. TLR agonists are effective immuomodulators in vaccine adjuvants for infectious diseases and cancer immunotherapy. In exploring hydrophilic small molecules of TLR7 ligands using the cell-targeted property of a vaccine adjuvant, we conjugated 1V209, a small TLR7 ligand molecule, with various low or middle molecular weight sugar molecules that work as carriers. The sugar-conjugated 1V209 derivatives showed increased water solubility and higher immunostimulatory activity in both mouse and human cells compared to unmodified 1V209. The improved immunostimulatory potency of sugar-conjugates was attenuated by an inhibitor of endocytic process, cytochalasin D, suggesting that conjugation of sugar moieties may enhance the uptake of TLR7 ligand into the endosomal compartment. Collectively our results support that sugar-conjugated TLR7 ligands are applicable to novel drugs for cancer and vaccine therapy.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Baba A,Wakao M,Shinchi H,Chan M,Hayashi T,Yao S,Cottam HB,Carson DA,Suda Y

doi

10.1016/j.bmcl.2019.126840

subject

Has Abstract

pub_date

2020-02-01 00:00:00

pages

126840

issue

3

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(19)30812-1

journal_volume

30

pub_type

杂志文章

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