Synthesis and evaluation of redox-sensitive gonadotropin-releasing hormone receptor-targeting peptide conjugates

被引：4

作者：

Dai, Yuxuan ^{[1
]}

Yue, Na ^{[1
]}

Liu, Chunxia ^{[1
]}

Cai, Xingguang ^{[1
]}

Su, Xin ^{[1
]}

Bi, Xinzhou ^{[1
]}

Li, Qifei ^{[1
]}

Li, Chengye ^{[1
]}

Huang, Wenlong ^{[1
,2
]}

Qian, Hai ^{[1
,2
]}

机构：

[1] China Pharmaceut Univ, Ctr Drug Discovery, State Key Lab Nat Med, 24 Tongjiaxiang, Nanjing 210009, Jiangsu, Peoples R China

[2] China Pharmaceut Univ, Jiangsu Key Lab Drug Discovery Metab Dis, 24 Tongjiaxiang, Nanjing 210009, Jiangsu, Peoples R China

来源：

BIOORGANIC CHEMISTRY | 2019年 / 88卷

基金：

中国国家自然科学基金;

关键词：

Lytic peptides; Redox-sensitive; Membranolytic; Apoptosis; CANCER; PRODRUG; RICH; ACTIVATION; MECHANISMS; RESISTANCE; ARGININE; THERAPY; LYSINE;

D O I：

10.1016/j.bioorg.2019.102945

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Lytic peptides have been demonstrated to exhibit obvious advantages in cancer therapy with binding ability toward tumor cells via electrostatic attractions, which are lack of active targeting and aggregation to tumor tissue. In the present study, five conjugated lytic peptides were redesigned and constructed to target gonadotropin releasing hormone receptors (GnRHr), meanwhile, the disulfide bridge was introduced to achieve redox sensitive delivery based on the experience from the preliminary work of lytic peptides P3 and P7. YX-1, was considered to be the most promising for in-depth study. YX-1 possessed high potency (IC50 = 3.16 +/- 0.3 mu M), low hemolytic effect, and cell membrane permeability in human A2780 ovarian cancer cells. Moreover, YX-1 had prominent pro-apoptotic activity by activating the mitochondria-cytochrome c-caspase apoptotic pathway. The study yielded the conjugate YX-1 with superior properties for antineoplastic activity, which makes it a promising potential candidate for targeting cancer therapy.

引用

页数：9