Peptide-nanoparticle ligation mediated by cutinase fusion for the development of cancer cell-targeted nanoconjugates

Bioconjugate Chemistry
Elisabetta GalbiatiDavide Prosperi

Abstract

The relationship between the positioning of ligands on the surface of nanoparticles and the structural features of nanoconjugates has been underestimated for a long time, albeit of primary importance to promote specific biological recognition at the nanoscale. In particular, it has been formerly observed that a proper molecular orientation can play a crucial role, first optimizing ligand immobilization onto the nanoparticles and, second, improving the targeting efficiency of the nanoconjugates. In this work, we present a novel strategy to afford peptide-oriented ligation using genetically modified cutinase fusion proteins, which combines the presence of a site-directed "capture" module based on an enzymatic unit and a "targeting" moiety consisting of the ligand terminal end of a genetically encoded polypeptide chain. As an example, the oriented presentation of U11 peptide, a sequence specific for the recognition of urokinase plasminogen activator receptor (uPAR), was achieved by enzyme-mediated conjugation with an irreversible inhibitor of cutinase, an alkylphosphonate p-nitrophenol ester linker, covalently bound to the surface of iron oxide nanoparticles. The targeting efficiency of the resulting protein-nanoparticle conjugate...Continue Reading

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Citations

Oct 27, 2015·International Journal of Molecular Sciences·Ujwal S PatilDouglas B Chrisey
Dec 17, 2016·Journal of Immunoassay & Immunochemistry·Justina O TamLee Gehrke
Sep 30, 2020·Chemical Communications : Chem Comm·Stefania GarbujoMiriam Colombo
Jun 27, 2020·Current Medicinal Chemistry·Soraia FernandesGiancarlo Forte
Feb 25, 2019·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Yuan HongHailin Ma

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