Facile Synthesis of Cyclic Peptide-Phthalocyanine Conjugates for Epidermal Growth Factor Receptor-Targeted Photodynamic Therapy

Jacky C.H. Chu, Wing Ping Fong, Clarence T.T. Wong, Dennis K.P. Ng

Research output: Journal article publicationJournal articleAcademic researchpeer-review

11 Citations (Scopus)

Abstract

A facile procedure for in situ peptide cyclization and phthalocyanine conjugation was developed by utilizing a bifunctional linker incorporated with a bis(bromomethyl)benzene unit and a cyclopentadiene moiety. These functional groups facilitated the nucleophilic substitution with the two cysteine residues of the linear peptides followed by the Diels-Alder reaction with the maleimide moiety attached to a zinc(II) phthalocyanine. With this approach, three cyclic peptide-phthalocyanine conjugates were prepared in 20-26% isolated yield via a one-pot procedure. One of the conjugates containing a cyclic form of the epidermal growth factor receptor (EGFR)-binding peptide sequence CMYIEALDKYAC displayed superior features as an advanced photosensitizer. It showed preferential uptake by two EGFR-positive cancer cell lines (HT29 and HCT116) compared with two EGFR-negative counterparts (HeLa and HEK293), resulting in significantly higher photocytotoxicity. Intravenous administration of this conjugate into HT29 tumor-bearing nude mice resulted in selective localization in tumor and effective inhibition of tumor growth upon photodynamic treatment.

Original languageEnglish
Pages (from-to)2064-2076
Number of pages13
JournalJournal of Medicinal Chemistry
Volume64
Issue number4
DOIs
Publication statusPublished - 25 Feb 2021
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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