Identification of a peptide-peptide binding motif in the coating of nab-paclitaxel nanoparticles with clinical antibodies: bevacizumab, rituximab, and trastuzumab

Scientific Reports
John T ButterfieldSvetomir N Markovic

Abstract

Antibody directed chemotherapy (ADC) takes advantage of the selectivity of the monoclonal antibody to increase the efficacy of the chemotherapeutic agent, while reducing toxicity. Previously we described three nab-paclitaxel (Abraxane) nanoparticles coated with commercial monoclonal antibodies. Identifying the binding sites responsible for these particles could allow reverse engineering of nab-paclitaxel binding antibodies, creating a modular platform for antibody directed chemotherapeutic nanoparticles. Herein, Biacore surface plasmon resonance is used to identify an antibody binding site, HSA Peptide 40, on human serum albumin with nanomolar affinity for all three monoclonal antibodies. This 18-mer peptide, which lies in Subdomain IIIA of human serum albumin, blocks binding of all three antibodies to nab-paclitaxel when added in excess. We furthermore show the complementary binding region on all three monoclonal antibodies to be the CDR H3 loop of the Fab region, and show that they all have nano to micromolar affinity for HSA Peptide 40 and nab-paclitaxel nanoparticles. The presented data identify the nature of the critical protein-protein interaction that enables antibody coating of nab-paclitaxel.

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Citations

Aug 22, 2018·Advanced Science·Seah Ling KuanTanja Weil
Jul 25, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Aline de Cristo Soares AlvesAdriana Raffin Pohlmann

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Methods Mentioned

BETA
Surface Plasmon Resonance
X-ray
dynamic light scattering
chip
reverse-phase chromatography
reverse phase chromatography
flow cytometry
Assay
chips

Software Mentioned

PEP
UCSF Chimera
PEPFOLD
Chimera MatchMaker
FOLD
Malvern NTA
Nanosight NTA
Clustal Omega
Biacore
MatchMaker

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