1. Identification of a peptide-peptide binding motif in the coating of nab-paclitaxel nanoparticles with clinical antibodies: bevacizumab, rituximab, and trastuzumab
- Author
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Daniel J. Knauer, Svetomir N. Markovic, Wendy K. Nevala, John T. Butterfield, and Hidong Kim
- Subjects
Models, Molecular ,0301 basic medicine ,medicine.drug_class ,lcsh:Medicine ,Nanoparticle ,Peptide ,Pharmacology ,Monoclonal antibody ,Article ,03 medical and health sciences ,Antineoplastic Agents, Immunological ,0302 clinical medicine ,Trastuzumab ,medicine ,Humans ,Binding site ,Surface plasmon resonance ,lcsh:Science ,Serum Albumin ,chemistry.chemical_classification ,Multidisciplinary ,biology ,lcsh:R ,Surface Plasmon Resonance ,Human serum albumin ,Bevacizumab ,030104 developmental biology ,Biochemistry ,chemistry ,030220 oncology & carcinogenesis ,biology.protein ,Nanoparticles ,lcsh:Q ,Binding Sites, Antibody ,Antibody ,Rituximab ,medicine.drug - 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.
- Published
- 2017