Antitumor activity of novel chimeric peptides derived from cyclinD/CDK4 and the protein transduction domain 4

被引：39

作者：

Wang, Haili ^{[1
,2
]}

Chen, Xi ^{[3
]}

Chen, Yanping ^{[1
]}

Sun, Lei ^{[1
]}

Li, Guodong ^{[1
]}

Zhai, Mingxia ^{[1
]}

Zhai, Wenjie ^{[1
]}

Kang, Qiaozhen ^{[1
]}

Gao, Yanfeng ^{[1
]}

Qi, Yuanming ^{[1
]}

机构：

[1] Zhengzhou Univ, Dept Bioengn, Zhengzhou 450001, Peoples R China

[2] Henan Prov Res Inst Family Planning, Eugen Genet Res Lab, Zhengzhou 450002, Peoples R China

[3] Harbin Med Univ, Affiliated Hosp 2, Harbin 150086, Peoples R China

来源：

AMINO ACIDS | 2013年 / 44卷 / 02期

基金：

中国国家自然科学基金;

关键词：

CyclinD; CDK4; Peptide; Antitumor; Apoptosis; GLYCOL) STAR COPOLYMER; CELL-CYCLE; IN-VIVO; DOWN-REGULATION; BREAST-CANCER; INHIBITORS; VITRO; CYTOTOXICITY; DESIGN; GROWTH;

D O I：

10.1007/s00726-012-1360-5

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

CyclinD1/CDK4 and cyclinD3/CDK4 complexes are key regulators of the cell progression and therefore constitute promising targets for the design of anticancer agents. In the present study, the key peptide motifs were selected from these two complexes. Chimeric peptides with these peptides conjugated to the protein transduction domain 4 (PTD4) were designed and synthesized. The chimeric peptides, PTD4-D1, PTD4-D3, PTD4-K4 exhibited significant anti-proliferation effects on cancer cell lines. These peptides could compete with the cyclinD/CDK4 complex and induce the G1/S phase arrest and apoptosis of cancer cells. In the tumor challenge experiment, these peptides showed potent antitumor effects with no significant side effects. Our results suggested that these peptides could be served as novel leading compounds with potent antitumor activity.

引用

页码：499 / 510

页数：12

共 42 条

[1]

REPLACE: A strategy for iterative design of cyclin-binding groove inhibitors [J].