title: Increasing Tumor Accessibility with Conjugatable Disulfide-Bridged Tumor-Penetrating Peptides for Cancer Diagnosis and Treatment.
abstract: 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.
authors.affiliation: 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.
authors.forename: Venkata Ramana
authors.initials: VR
authors.lastname: Kotamraju
authors.affiliation: Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
authors.forename: Shweta
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Department of Biomolecular Science and Engineering, University of California, Santa Barbara, Santa Barbara, CA, USA.
authors.forename: Poornima
authors.initials: P
authors.lastname: Kolhar
authors.affiliation: Department of Plant Sciences, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Lilach
authors.initials: L
authors.lastname: Agemy
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Santa Barbara, Santa Barbara, CA, USA.
authors.forename: James
authors.initials: J
authors.lastname: Pavlovich
authors.affiliation: 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.
authors.forename: Erkki
authors.initials: E
authors.lastname: Ruoslahti
keywords: conjugatable disulfide peptides; cyclic peptide conjugation nanoworm conjugates; homing peptides; oligonucleotide conjugates; tumor targeting; tumor-penetrating peptides