Increasing Tumor Accessibility with Conjugatable Disulfide-Bridged Tumor-Penetrating Peptides for Cancer Diagnosis and Treatment

Breast Cancer: Basic and Clinical Research

Original Research

Shweta Sharma¹  Venkata Ramana Kotamraju²  Erkki Ruoslahti²  Poornima Kolhar³  James Pavlovich⁴  Lilach Agemy⁵ 

[1] Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.;Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.;Department of Molecular, Cellular, and Developmental Biology, Center for Nanomedicine, University of California, Santa Barbara, Santa Barbara, CA, USA.;Department of Biomolecular Science and Engineering, University of California, Santa Barbara, Santa Barbara, CA, USA.;Department of Chemistry and Biochemistry, University of California, Santa Barbara, Santa Barbara, CA, USA.;Department of Plant Sciences, Weizmann Institute of Science, Rehovot, Israel.;

关键词: tumor targeting;    homing peptides;    tumor-penetrating peptides;    conjugatable disulfide peptides;    cyclic peptide conjugation nanoworm conjugates;    oligonucleotide conjugates;   

DOI  :  10.4137/BCBCR.S29426

 received in 2015-07-03, accepted in 2015-11-02,  发布年份 2015

来源: Sage Journals

【 摘 要 】

Tumor-homing peptides with tissue-penetrating properties increase the efficacy of targeted cancer therapy by delivering an anticancer agent to the tumor interior. LyP-1 (CGNKRTRGC) and iRGD (CRGDKGPDC) are founding members of this class of peptides. The presence of the cysteines forming the cyclizing disulfide bond complicates conjugation of these peptides with other molecules, such as drugs. Here, we report the synthesis of conjugatable disulfide-bridged peptides and their conjugation to biologically important molecules. We have synthesized the LyP-1, iRGD, and CRGDC (GACRGDCLGA) peptides with a cysteine or maleimidohexanoic acid added externally at N-terminus of the sequences. Subsequent conjugation to payloads yielded stable compounds in which the tumor-homing properties of the peptide and the biological activity of the payload were retained.

【 授权许可】

CC BY-NC   
© 2015 SAGE Publications.

【 图 表 】

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