High-performance sono/nano-catalytic system: FeO@Pd/CaCO-DTT core/shell nanostructures, a suitable alternative for traditional reducing agents for antibodies
Authors: Ali Salimi
Ehsan Zolfaghari
Maral Radmanesh
Hodjattallah Rabbani
Ramin Fazel
Ali Maleki
Reza Taheri-Ledari
Journal: Ultrasonics sonochemistry (2020)
Discipline: CHEMISTRY
Keywords: Antibody reduction; Dithiothreitol; Herceptin; Magnetic nanoparticles; Sonochemistry
Affiliations: Catalysts and Organic Synthesis Research Laboratory, Department of Chemistry, Iran University of Science and Technology, Tehran 16846-13114, Iran., Catalysts and Organic Synthesis Research Laboratory, Department of Chemistry, Iran University of Science and Technology, Tehran 16846-13114, Iran. Electronic address: ., Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR, Tehran, Iran., Livogen Pharmed, Research and Innovation Center, Tehran, Iran.

Abstract:  Herein, a novel heterogeneous nanoscale reducing agent for antibody cleavage, made of iron oxide nanoparticles, silica network, palladium on calcium carbonate (10%), and dithiothreitol (Fe3O4@Pd/CaCO3-DTT), is presented as a substantial alternative for traditional homogeneous analogues. Conventionally, antibody fragmentation is accomplished using reducing agents and proteases that digest or cleave certain portions of the immunoglobulin protein structure to provide active thiol sites for drug tagging aims. Then, dialysis process is needed to separate excess chemical structures and purify the reduced antibody. In this work, we have made an effort to design a suitable heterogeneous tool for protein cleavage and skip the dialysis process for purification of the reduced antibody. In this regard, firstly, various preparation methods including microwave irradiation, reflux and ultrasonication have been precisely compared, and it has been proven that the best result is obtained through 10 min ultrasound (US) irradiation using an US bath with 50 KHz frequency and 200 W L-1 power density. Then, all the necessary structural analyses have been done and thoroughly interpreted for the final product. Afterward, the catalytic performance of Fe3O4@Pd/CaCO3-DTT nanoscale system in the presence of US waves (50 KHz, 200 W) has been monitored using some disulphide derivatives. The NPs could be conveniently separated from the mixture through their substantial paramagnetic property. Thus, dialysis process in which various types of membranes are used is practically jumped after the reduction process. In this work, this is clearly demonstrated that there is a constructive synergistic effect between US waves and prepared Fe3O4@Pd/CaCO3-DTT nanoscale reducing agent. Ultimately, trastuzumab (anti HER-2) antibody has been used to test the performance of the prepared Fe3O4@Pd/CaCO3-DTT NPs in a real protein reduction reaction. 

Retracted: No

PubPeer comments:
 2018 retraction notice. http: www.jbc.org content 293 10 3589  VOLUME 284 (2009) PAGES 455u2013464 This article has been withdrawn by the authors. In June 2017, the Journal raised questions about Figs. 1A and 5D. The original data and originally submitted figures were not available for evaluation. The authors were able to locate data for a repeat experiment conducted at the time of the original work for Fig. 1A and offered to prepare a new figure. The authors also offered to repeat the experiment reflected in Fig. 5D and to publish an amended figure. The Journal declined both offers, a decision with which the authors disagree. The authors stand by the reproducibility of the experimental data and the conclusions of the paper. The paper, with confirmatory data supporting the results, can be obtained by contacting the authors. u00a9 2018 by The American Society for Biochemistry and Molecular Biology, Inc. , 
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