Design and synthesis of novel dual-cyclic RGD peptides for αvβ3 integrin targeting

Junjie Liu; Xiaozhong Cheng; Xiaobo Tian; Dongliang Guan; Jiwei Ao; Zhimeng Wu; Wei Huang; Zhiping Le

doi:10.1016/j.bmcl.2019.01.043

Design and synthesis of novel dual-cyclic RGD peptides for α_vβ₃ integrin targeting

Bioorg Med Chem Lett. 2019 Apr 1;29(7):896-900. doi: 10.1016/j.bmcl.2019.01.043. Epub 2019 Feb 1.

Authors

Junjie Liu¹, Xiaozhong Cheng², Xiaobo Tian¹, Dongliang Guan³, Jiwei Ao⁴, Zhimeng Wu⁵, Wei Huang⁶, Zhiping Le⁷

Affiliations

¹ Department of Chemistry, Nanchang University, 999 Xuefu Avenue, Nanchang 330031, PR China; CAS Key Laboratory of Receptor Research, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Pudong, Shanghai 201203, PR China.
² Key Laboratory of Carbohydrate Chemistry & Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, PR China.
³ CAS Key Laboratory of Receptor Research, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Pudong, Shanghai 201203, PR China; University of Chinese Academy of Sciences, No.19A Yuquan Road, Beijing 100049, PR China.
⁴ CAS Key Laboratory of Receptor Research, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Pudong, Shanghai 201203, PR China.
⁵ Key Laboratory of Carbohydrate Chemistry & Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, PR China. Electronic address: zwu@jiangnan.edu.cn.
⁶ CAS Key Laboratory of Receptor Research, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Pudong, Shanghai 201203, PR China; University of Chinese Academy of Sciences, No.19A Yuquan Road, Beijing 100049, PR China. Electronic address: huangwei@simm.ac.cn.
⁷ Department of Chemistry, Nanchang University, 999 Xuefu Avenue, Nanchang 330031, PR China. Electronic address: zple@ncu.edu.cn.

PMID: 30732943
DOI: 10.1016/j.bmcl.2019.01.043

Abstract

The specific binding of RGD cyclic peptide with integrin α_vβ₃ attracts great research interest for tumor-targeting drug delivery. Herein, we designed and synthesized a series of dual-ring RGD-peptide derivatives as a drug carrier for α_vβ₃ targeting. Three novel peptides showed excellent cell adhesion inhibition effect, in which, P3 exhibited 7-fold enhancement in IC₅₀ compared with cyclo(RGDfK). Drug-loaded cytotoxicity experiment and imaging experiment indicated that such dual-cyclic RGD peptides have good tumor targeting effects. This work provides a new strategy for the design of novel RGD peptides.

Keywords: Adhesion inhibition; Cyclo(RGDfK); RGD cyclic peptide; Tumor-targeting; α(v)β(3) integrin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology
Cell Adhesion / drug effects
Cell Line, Tumor
Cell Survival / drug effects
Drug Design
Humans
Integrin alphaVbeta3 / metabolism*
Oligopeptides / chemical synthesis*
Oligopeptides / chemistry
Oligopeptides / pharmacology*
Protein Conformation

Substances

Antineoplastic Agents
Integrin alphaVbeta3
Oligopeptides
arginyl-glycyl-aspartic acid