Antitumor activity of novel chimeric peptides derived from cyclinD/CDK4 and the protein transduction domain 4.
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.
Department of Bioengineering, Zhengzhou University, 100 Science Road, Zhengzhou 450001, China.
Haili
H
Wang
Xi
X
Chen
Yanping
Y
Chen
Lei
L
Sun
Guodong
G
Li
Mingxia
M
Zhai
Wenjie
W
Zhai
Qiaozhen
Q
Kang
Yanfeng
Y
Gao
Yuanming
Y
Qi
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D019938:Cyclin D1 / Q000235:genetics*; D056743:Cyclin D3 / Q000235:genetics*; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D010446:Peptide Fragments / Q000235:genetics*; D010455:Peptides / Q000138:chemical synthesis / Q000235:genetics / Q000494:pharmacology*; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics*
D000970:Antineoplastic Agents; D056743:Cyclin D3; D010446:Peptide Fragments; D010455:Peptides; C575807:Tat peptide (47-59), HIV-1; D054322:tat Gene Products, Human Immunodeficiency Virus; D019938:Cyclin D1; D051358:Cyclin-Dependent Kinase 4