Discovery of peptide inhibitors targeting human programmed death 1 (PD-1) receptor

被引：49

作者：

Li, Qiao ^{[1
]}

Quan, Lina ^{[1
]}

Lyu, Jiankun ^{[1
]}

He, Zenghui ^{[1
]}

Wang, Xia ^{[1
]}

Meng, Jiajia ^{[1
]}

Zhao, Zhenjiang ^{[1
]}

Zhu, Lili ^{[1
]}

Liu, Xiaofeng ^{[1
]}

Li, Honglin ^{[1
]}

机构：

[1] East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China

来源：

ONCOTARGET | 2016年 / 7卷 / 40期

基金：

中国国家自然科学基金;

关键词：

immunotherapy; human programmed death 1; peptide inhibitor; protein-protein interactions (PPIs); de novo peptide design; CANCER-IMMUNOTHERAPY; HOT-SPOTS; WEB SERVER; BINDING; LIGANDS; ENERGY; DETERMINANTS; SIMULATION; EXPRESSION; PREDICTION;

D O I：

10.18632/oncotarget.11274

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Blocking the interaction of human programmed death 1 (hPD-1) and its ligand hPD-L1 has been a promising immunotherapy in cancer treatment. In this paper, using a computational de novo peptide design method, we designed several hPD-1 binding peptides. The most potent peptide Ar5Y_4 showed a KD value of 1.38 +/- 0.39 mu M, comparable to the binding affinity of the cognate hPD-L1. A Surface Plasmon Resonance (SPR) competitive binding assay result indicated that Ar5Y_4 could inhibit the interaction of hPD-1/hPD-L1. Moreover, Ar5Y_4 could restore the function of Jurkat T cells which had been suppressed by stimulated HCT116 cells. Peptides described in this paper provide promising biologic candidates for cancer immunotherapy or diagnostics.

引用

页码：64967 / 64976

页数：10

共 52 条

[1] [Anonymous], PYMOL MOL GRAPHICS S
[2] The Protein Data Bank
Berman, HM
Westbrook, J
Feng, Z
Gilliland, G
Bhat, TN
Weissig, H
Shindyalov, IN
Bourne, PE
[J]. NUCLEIC ACIDS RESEARCH, 2000, 28 (01) : 235 - 242
[3] Case D. A., 2015, AMBER
[4] The Amber biomolecular simulation programs
Case, DA
Cheatham, TE
Darden, T
Gohlke, H
Luo, R
Merz, KM
Onufriev, A
Simmerling, C
Wang, B
Woods, RJ
[J]. JOURNAL OF COMPUTATIONAL CHEMISTRY, 2005, 26 (16) : 1668 - 1688
[5] Blocking of the PD-1/PD-L1 Interaction by a D-Peptide Antagonist for Cancer Immunotherapy
Chang, Hao-Nan
Liu, Bei-Yuan
Qi, Yun-Kun
Zhou, Yang
Chen, Yan-Ping
Pan, Kai-Mai
Li, Wen-Wen
Zhou, Xiu-Man
Ma, Wei-Wei
Fu, Cai-Yun
Qi, Yuan-Ming
Liu, Lei
Gao, Yan-Feng
[J]. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2015, 54 (40) : 11760 - 11764
[6] A HOT-SPOT OF BINDING-ENERGY IN A HORMONE-RECEPTOR INTERFACE
CLACKSON, T
WELLS, JA
[J]. SCIENCE, 1995, 267 (5196) : 383 - 386
[7] Relaxation of backbone bond geometry improves protein energy landscape modeling
Conway, Patrick
Tyka, Michael D.
DiMaio, Frank
Konerding, David E.
Baker, David
[J]. PROTEIN SCIENCE, 2014, 23 (01) : 47 - 55
[8] Resultanta and loop closure
Coutsias, EA
Seok, C
Wester, MJ
Dill, KA
[J]. INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, 2006, 106 (01) : 176 - 189
[9] A mutational analysis of the binding of two different proteins to the same antibody
DallAcqua, W
Goldman, ER
Eisenstein, E
Mariuzza, RA
[J]. BIOCHEMISTRY, 1996, 35 (30) : 9667 - 9676
[10] PARTICLE MESH EWALD - AN N.LOG(N) METHOD FOR EWALD SUMS IN LARGE SYSTEMS
DARDEN, T
YORK, D
PEDERSEN, L
[J]. JOURNAL OF CHEMICAL PHYSICS, 1993, 98 (12) : 10089 - 10092

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