Blockade of the checkpoint PD-1 by its ligand PD-L1 and the immuno-oncological drugs pembrolizumab and nivolumab

Literature Information

Publication Date 2021-09-13
DOI 10.1039/D1CP03064G
Impact Factor 3.676
Authors

J. X. Lima Neto, U. L. Fulco, E. L. Albuquerque


View Original

Abstract

We investigate the interaction between the programmed cell death protein 1 (PD-1) and the programmed cell death ligand 1 (PD-L1), as well as the immuno-oncological drugs pembrolizumab (PEM), and nivolumab (NIV), through quantum chemistry methods based on the Density Functional Theory (DFT) and the molecular fractionation with conjugate caps (MFCC) scheme, in order to map their hot-spot regions. Our results showed that the total interaction energy order of the three complexes is in good agreement with the experimental binding affinity order: PD-1/PEM > PD-1/NIV > PD-1/PD-L1. Besides, a detailed investigation revealed the energetically most relevant residue–residue pairs-interaction for each complex. Our computational results give a better understanding of the interaction mechanism between the protein PD-1 and its ligands (natural and inhibitors), unleashing the immune surveillance to destroy the cancer cells by decreasing their immune evasion. They are also an efficient alternative towards the development of new small-molecules and antibody-based drugs, pointing out to new treatments for cancer therapy.

Related Literature

Metal-free synthesis of imino-disaccharides and calix-iminosugars by photoinduced radical thiol–ene coupling (TEC)

Renaud Zelli, Pascal Dumy, Alberto Marra

2020-02-21 Communication

DOI: 10.1039/D0OB00198H

Construction of key building blocks towards the synthesis of cortistatins

Satrajit Indu, Rahul D. Telore, Krishna P. Kaliappan

2020-03-02 Paper

DOI: 10.1039/D0OB00170H

Base-controlled divergent synthesis of vinyl sulfones from (benzylsulfonyl)benzenes and paraformaldehyde

Fuhong Xiao, Yangling Hu, Huawen Huang, Fen Xu, Guo-Jun Deng

2020-04-22 Paper

DOI: 10.1039/D0OB00362J

Structure elucidation of bacterial nonribosomal lipopeptides

Sebastian Götze, Pierre Stallforth

2020-02-03 Review Article

DOI: 10.1039/C9OB02539A

Front cover

Cover

DOI: 10.1039/D0OB90044C

A visible-light-induced “on–off” one-pot synthesis of 3-arylacetylene coumarins with AIE properties

Xinjie Wu, Ming Jia, Mengmeng Huang, Jung Keun Kim, Zheng Zhao, Junkai Liu, Jinhu Xi, Yabo Li, Yangjie Wu

2020-04-08 Paper

DOI: 10.1039/D0OB00479K

The effect of spermidine on guanine decomposition via photoinduced electron transfer in DNA

Mayu Esumi, Shunsuke Sakurai, Makiko Tanaka

2019-11-27 Communication

DOI: 10.1039/C9OB01860C

You might also like

Compound Q&A

What regulatory guidelines apply to 6-Bromo-2-methylimidazo[1,2-a]pyrimidine (CAS: 1111638-05-1)?

6-Bromo-2-methylimidazo[1,2-a]pyrimidine (CAS: 1111638-05-1) falls under various...

1111638-05-16-Bromo-2-methylimid...
Compound Q&A

Are there alternatives to 1-Pyrrolidineethanol, β-methyl-α-phenyl-, (αS,βR) (CAS: 123620-80-4) in synthesis?

While there are no direct alternatives, similar compounds like 1-Pyrrolidineetha...

123620-80-41-Pyrrolidineethanol...
Compound Q&A

Is 4-Methyl-2,6-bis(2-methyl-2-propanyl)phenyl methylcarbamate (CAS: 1918-11-2) safe?

4-Methyl-2,6-bis(2-methyl-2-propanyl)phenyl methylcarbamate (CAS: 1918-11-2) is ...

1918-11-24-Methyl-2,6-bis(2-m...
Compound Q&A

How should 2-(3-Bromo-4-fluorophenyl)-1,3-dioxolane (CAS: 77771-04-1) be stored?

2-(3-Bromo-4-fluorophenyl)-1,3-dioxolane (CAS: 77771-04-1) should be stored in a...

77771-04-12-(3-Bromo-4-fluorop...
Compound Q&A

What are the physical and chemical properties of 4,5,6,7-Tetrahydro-1H-indazole hydrochloride (CAS: 18161-11-0)?

4,5,6,7-Tetrahydro-1H-indazole hydrochloride is a white crystalline solid with a...

18161-11-04,5,6,7-Tetrahydro-1...
Compound Q&A

What is (2R)-1-Methoxy-3-phenyl-2-propanamine (CAS: 59919-07-2)?

(2R)-1-Methoxy-3-phenyl-2-propanamine is a chiral organic compound with the CAS ...

59919-07-2(2R)-1-Methoxy-3-phe...
Compound Q&A

What industries use Ethyl 1-(1-phenylethyl)-1H-imidazole-5-carboxylate (CAS: 56649-47-9)?

Ethyl 1-(1-phenylethyl)-1H-imidazole-5-carboxylate is used in various industries...

56649-47-9Ethyl 1-(1-phenyleth...
Compound Q&A

What regulatory guidelines apply to 4-[(1E,3S)-1-(4-Hydroxyphenyl)-1,4-pentadien-3-yl]phenol (CAS: 17676-24-3)?

4-[(1E,3S)-1-(4-Hydroxyphenyl)-1,4-pentadien-3-yl]phenol (CAS: 17676-24-3) falls...

17676-24-34-[(1E,3S)-1-(4-Hydr...
Compound Q&A

What industries use (S)-3-Amino-5-phenylpentanoic acid hydrochloride (CAS: 331846-97-0)?

(S)-3-Amino-5-phenylpentanoic acid hydrochloride is primarily used in the pharma...

331846-97-0(S)-3-Amino-5-phenyl...
Compound Q&A

How is 7-methoxy-1-benzothiophene-2-carboxylic acid (CAS: 88791-07-5) typically synthesized?

7-Methoxy-1-benzothiophene-2-carboxylic acid is typically synthesized by reactin...

88791-07-57-methoxy-1-benzothi...

Source Journal

Physical Chemistry Chemical Physics

Physical Chemistry Chemical Physics
CiteScore: 5.5
Self-citation Rate: 10.3%
Articles per Year: 3036

Physical Chemistry Chemical Physics (PCCP) is an international journal co-owned by 19 physical chemistry and physics societies from around the world. This journal publishes original, cutting-edge research in physical chemistry, chemical physics and biophysical chemistry. To be suitable for publication in PCCP, articles must include significant innovation and/or insight into physical chemistry; this is the most important criterion that reviewers and Editors will judge against when evaluating submissions. The journal has a broad scope and welcomes contributions spanning experiment, theory, computation and data science. Topical coverage includes spectroscopy, dynamics, kinetics, statistical mechanics, thermodynamics, electrochemistry, catalysis, surface science, quantum mechanics, quantum computing and machine learning. Interdisciplinary research areas such as polymers and soft matter, materials, nanoscience, energy, surfaces/interfaces, and biophysical chemistry are welcomed if they demonstrate significant innovation and/or insight into physical chemistry. Joined experimental/theoretical studies are particularly appreciated when complementary and based on up-to-date approaches.

Recommended Compounds

Recommended Suppliers

Disclaimer
This page provides academic journal information for reference and research purposes only. We are not affiliated with any journal publishers and do not handle publication submissions. For publication-related inquiries, please contact the respective journal publishers directly.
If you notice any inaccuracies in the information displayed, please contact us at support@chemtradehub.com. We will promptly review and address your concerns.