NGR-peptide-drug conjugates with dual targeting properties

Kata Nóra Enyedi, Szilárd Tóth, G. Szakács, G. Mező

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Peptides containing the asparagine-glycine-arginine (NGR) motif are recognized by CD13/aminopeptidase N (APN) receptor isoforms that are selectively overexpressed in tumor neovasculature. Spontaneous decomposition of NGR peptides can result in isoAsp derivatives, which are recognized by RGD-binding integrins that are essential for tumor metastasis. Peptides binding to CD13 and RGD-binding integrins provide tumor-homing, which can be exploited for dual targeted delivery of anticancer drugs. We synthesized small cyclic NGR peptide-daunomycin conjugates using NGR peptides of varying stability (c[KNGRE]-NH2, Ac-c[CNGRC]-NH2 and the thioether bond containing c[CH2-CO-NGRC]-NH2, c[CH2-COKNGRC]-NH2). The cytotoxic effect of the novel cyclic NGR peptide-Dau conjugates were examined in vitro on CD13 positive HT-1080 (human fibrosarcoma) and CD13 negative HT-29 (human colon adenocarcinoma) cell lines. Our results confirm the influence of structure on the antitumor activity and dual acting properties of the conjugates. Attachment of the drug through an enzyme-labile spacer to the C-terminus of cyclic NGR peptide resulted in higher antitumor activity on both CD13 positive and negative cells as compared to the branching versions.

Original languageEnglish
Article numbere0178632
JournalPLoS One
Volume12
Issue number6
DOIs
Publication statusPublished - Jun 1 2017

Fingerprint

NGR peptide
cyclic peptides
Cyclic Peptides
peptides
drugs
integrins
Tumors
Pharmaceutical Preparations
neoplasms
Integrins
membrane alanyl aminopeptidase
fibrosarcoma
antineoplastic agents
CD13 Antigens
asparagine
adenocarcinoma
Neoplasms
Peptides
glycine (amino acid)
Daunorubicin

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

NGR-peptide-drug conjugates with dual targeting properties. / Enyedi, Kata Nóra; Tóth, Szilárd; Szakács, G.; Mező, G.

In: PLoS One, Vol. 12, No. 6, e0178632, 01.06.2017.

Research output: Contribution to journalArticle

Enyedi, Kata Nóra ; Tóth, Szilárd ; Szakács, G. ; Mező, G. / NGR-peptide-drug conjugates with dual targeting properties. In: PLoS One. 2017 ; Vol. 12, No. 6.
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