2. Academic Validation
  3. Pep5-based antitumor peptides containing multifunctional fragments with enhanced activity and synergistic effect

Pep5-based antitumor peptides containing multifunctional fragments with enhanced activity and synergistic effect

  • Eur J Med Chem. 2022 Jul 5:237:114320. doi: 10.1016/j.ejmech.2022.114320.
Taoran Wang 1,  Long Tian 2,  Qin Cheng 3,  Siliang Feng 1,  Han Zhang 1,  Zhibing Zheng 1,  Yang Liu 4,  Maosheng Cheng 5,  Zhao Meng 6,  Qingbin Meng 7
Affiliations

Affiliations

  • 1 State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, China.
  • 2 State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, China; Key Laboratory of Structure-Based Drug Design and Discovery of the Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, China.
  • 3 State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, China; Key Laboratory of Natural Resources and Functional Molecules of the Changbai Mountain, Affiliated Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin, 133002, China.
  • 4 Key Laboratory of Structure-Based Drug Design and Discovery of the Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, China.
  • 5 Key Laboratory of Structure-Based Drug Design and Discovery of the Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, China. Electronic address: mscheng@263.net.
  • 6 State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, China. Electronic address: mengzhao900817@163.com.
  • 7 State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, China; Key Laboratory of Natural Resources and Functional Molecules of the Changbai Mountain, Affiliated Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin, 133002, China. Electronic address: nankaimqb@sina.com.
PMID: 35452935 DOI: 10.1016/j.ejmech.2022.114320
Abstract

In this study, we designed a series of hybrid Peptides based on pep5-TAT (P-05), comprising antitumor segment (pep5), endosomal escape segment ((LLHH)3) and cell penetrating/membrane disrupting segment (TAT, R9, sC182). These Peptides exhibited remarkable antitumor activity towards tumor cells (HepG2, A549). Among them, the IC50 values of peptide P-09 were 4.0 and 4.8 times lower than those of P-05 in HepG2 and A549 cells, respectively. It was proved that P-09 could enter tumor cells through endocytosis and direct penetration and induce the Apoptosis and necrosis. The antitumor effects were attributed to the synergistic effect of membrane disruption and Proteasome inhibition, which occurred during and after the cellular entry, respectively. The whole process was accompanied by excessive ROS production. In vivo, P-09 exhibited enhanced ability to inhibit the growth of HepG2 subcutaneous tumor xenografts than P-05 in nude mice. In brief, this work provided valuable insights into the design of peptide-based antitumor agents with synergistic antitumor effects.

Keywords

Membrane disruption; Proteasome inhibition; Synergistic effect; pep5-based peptides.

Figures
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z