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Multimeric Presentation of RGD Peptidomimetics Enhances Integrin Binding and Tumor Cell Uptake
Author(s) -
Pina Arianna,
Kadri Malika,
Arosio Daniela,
Dal Corso Alberto,
Coll JeanLuc,
Gennari Cesare,
Boturyn Didier
Publication year - 2020
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202001115
Subject(s) - peptidomimetic , integrin , endocytosis , chemistry , scaffold , in vivo , drug delivery , cell , microbiology and biotechnology , biophysics , cancer research , biochemistry , peptide , biology , medicine , biomedical engineering , organic chemistry
The use of multimeric ligands is considered as a promising strategy to improve tumor targeting for diagnosis and therapy. Herein, tetrameric RGD (Arg‐Gly‐Asp) peptidomimetics were designed to target α v β 3 integrin‐expressing tumor cells. These compounds were prepared by an oxime chemoselective assembly of cyclo (DKP‐RGD) ligands and a cyclodecapeptide scaffold, which allows a tetrameric presentation. The resulting tetrameric RGD peptidomimetics were shown to improve α v β 3 integrin binding compared with the monomeric form. Interestingly, these compounds were also able to enhance tumor cell endocytosis in the same way as tetrameric RGD peptides. Altogether, the results show the potential of the tetrameric cyclo (DKP‐RGD) ligands for in vivo imaging and drug delivery.