Conjugation of biphenyl groups with poly(ethylene glycol) to enhance inhibitory effects on the PD-1/PD-L1 immune checkpoint interaction

2020 ◽  
Vol 8 (44) ◽  
pp. 10162-10171
Author(s):  
Eun-Hye Kim ◽  
Boyang Ning ◽  
Masuki Kawamoto ◽  
Hideyuki Miyatake ◽  
Eiry Kobatake ◽  
...  
Keyword(s):  
Ethylene Glycol ◽  
Small Molecule ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Inhibitory Effect ◽  
Inhibitory Effects ◽  
Poly Ethylene Glycol ◽  
Poly Ethylene ◽  
Multivalent Effect

Inhibitory effect of small molecule immune checkpoint inhibitors on the PD-1/PD-L1 immune checkpoint interaction was enhanced by the multivalent effect through the conjugation of branched PEG.

scholarly journals Enhanced user-control of small molecule drug release from a poly(ethylene glycol) hydrogel via azobenzene/cyclodextrin complex tethers

2016 ◽  
Vol 4 (6) ◽  
pp. 1035-1039 ◽  
Author(s):  
Eric M. Nehls ◽  
Adrianne M. Rosales ◽  
Kristi S. Anseth
Keyword(s):  
Drug Release ◽  
Ethylene Glycol ◽  
Small Molecule ◽  
Release Rate ◽  
Poly Ethylene Glycol ◽  
Small Peptide ◽  
Cyclodextrin Complex ◽  
Small Molecule Drug ◽  
Poly Ethylene ◽  
Host Chemistry

Photoresponsive azobenzene–cyclodextrin guest–host chemistry can be used to control the release rate of a small peptide from a PEG hydrogel with light.

Poly(ethylene glycol) hybrids of RGD and YIGSR and their inhibitory effect on experimental metastasis

Peptides ◽  
1993 ◽  
pp. 120-122 ◽  
Author(s):  
Koichi Kawasaki ◽  
Yuko Yamasiro ◽  
Machiko Namikawa ◽  
Tomohiro Murakami ◽  
Toyohiko Mizuta ◽  
...  
Keyword(s):  
Ethylene Glycol ◽  
Inhibitory Effect ◽  
Experimental Metastasis ◽  
Poly Ethylene Glycol ◽  
Poly Ethylene

scholarly journals Solid-state mechanochemical ω-functionalization of poly(ethylene glycol)

2017 ◽  
Vol 13 ◽  
pp. 1963-1968 ◽  
Author(s):  
Michael Y Malca ◽  
Pierre-Olivier Ferko ◽  
Tomislav Friščić ◽  
Audrey Moores
Keyword(s):  
Solid State ◽  
Carboxylic Acid ◽  
Ethylene Glycol ◽  
Small Molecule ◽  
Poly Ethylene Glycol ◽  
Chemical Manufacturing ◽  
Pharmacokinetic Profiles ◽  
Wide Range ◽  
Poly Ethylene ◽  
Peg Functionalization

Poly(ethylene glycol) (PEG) is a linear polymer with a wide range of applications in chemical manufacturing, drug development and nanotechnology. PEG derivatives are being increasingly used to covalently modify small molecule and peptide drugs, as well as bioactive nanomaterials in order to improve solubility in biological serum, reduce immunogenicity, and enhance pharmacokinetic profiles. Herein we present the development of mechanochemical procedures for PEG functionalization without the need for bulk solvents, offering a cleaner and more sustainable alternative to existing solution-based PEG procedures. The herein presented mechanochemical procedures enable rapid and solvent-free derivatization of PEG with tosyl, bromide, thiol, carboxylic acid or amine functionalities in good to quantitative yields and with no polymer chain oligomerization, proving the versatility of the method.

scholarly journals Development of Indole Alkaloid-Type Dual Immune Checkpoint Inhibitors Against CTLA-4 and PD-L1 Based on Diversity-Enhanced Extracts

2021 ◽  
Vol 9 ◽  
Author(s):  
Yoshihide Suzuki ◽  
Keisuke Ichinohe ◽  
Akihiro Sugawara ◽  
Shinya Kida ◽  
Shinya Murase ◽  
...  
Keyword(s):  
Gene Expression ◽  
Small Molecules ◽  
Small Molecule ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Indole Alkaloid ◽  
Cell Penetration ◽  
Manufacturing Costs ◽  
Blocking Antibodies

Cancer immunotherapy involves the use of the immune system for cancer treatment. Recently, immune checkpoint-blocking antibodies have become integral for the treatment of some cancers. However, small molecules exhibit advantages over monoclonal antibody drugs, such as cell penetration, long half-life, and low manufacturing costs, and the possibility of oral administration. Thus, it is imperative to develop small-molecule immune checkpoint inhibitors. Previously, we have screened a library of synthetic indole-alkaloid-type compounds, which are produced by diversity-enhanced extracts of Japanese cornelian cherry, and reported that an unnatural pentacyclic compound inhibits CTLA-4 gene expression. In this study, immune checkpoint inhibitors with increased potency were developed by introducing substituents and conversion of functional groups based on the unnatural pentacyclic compound. The developed compounds suppressed not only CTLA-4 and PD-L1 gene expression but also protein expression on the cell surface. Their efficacy was not as potent as that of the existing small-molecule immune checkpoint inhibitors, but, to the best of our knowledge, the developed compounds are the first reported dual small-molecule inhibitors of CTLA-4 and PD-L1.

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