Novel Hybrid Compound of a Plinabulin Prodrug with an IgG Binding Peptide for Generating a Tumor Selective Noncovalent-Type Antibody–Drug Conjugate

Muguruma, Kyohei; Yakushiji, Fumika; Kawamata, Ryosuke; Akiyama, Daichi; Arima, Risako; Shirasaka, Takuya; Kikkawa, Yamato; Taguchi, Akihiro; Takayama, Kentaro; Fukuhara, Takeshi; Watabe, Tetsuro; Ito, Yuji; Hayashi, Yoshio

doi:10.1021/acs.bioconjchem.6b00149

Cited by 23 publications

(19 citation statements)

References 32 publications

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“…Muguruma and coworkers recently reported the development of a non-covalent antibody-drug conjugate (NC-ADC) based on the synthetic 33-mer Fc-binding peptide Z33 (Scheme 1) [75]. In their approach, the anticancer agent plinabulin was covalently linked to Z33 using Click chemistry.…”

Section: Modern Applications Of Immunoglobulin Binding Ligandsmentioning

confidence: 99%

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Fc-Binding Ligands of Immunoglobulin G: An Overview of High Affinity Proteins and Peptides

2016

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The rapidly increasing application of antibodies has inspired the development of several novel methods to isolate and target antibodies using smart biomaterials that mimic the binding of Fc-receptors to antibodies. The Fc-binding domain of antibodies is the primary binding site for e.g., effector proteins and secondary antibodies, whereas antigens bind to the Fab region. Protein A, G, and L, surface proteins expressed by pathogenic bacteria, are well known to bind immunoglobulin and have been widely exploited in antibody purification strategies. Several difficulties are encountered when bacterial proteins are used in antibody research and application. One of the major obstacles hampering the use of bacterial proteins is sample contamination with trace amounts of these proteins, which can invoke an immune response in the host. Many research groups actively develop synthetic ligands that are able to selectively and strongly bind to antibodies. Among the reported ligands, peptides that bind to the Fc-domain of antibodies are attractive tools in antibody research. Besides their use as high affinity ligands in antibody purification chromatography, Fc-binding peptides are applied e.g., to localize antibodies on nanomaterials and to increase the half-life of proteins in serum. In this review, recent developments of Fc-binding peptides are presented and their binding characteristics and diverse applications are discussed.

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Section: Modern Applications Of Immunoglobulin Binding Ligandsmentioning

confidence: 99%

Section: Figures Scheme and Tablesmentioning

confidence: 99%

Fc-Binding Ligands of Immunoglobulin G: An Overview of High Affinity Proteins and Peptides

2016

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“…Alternatively, when IgG-binding peptides containing catalysts induced the conjugation reaction between payload and antibody as previously cited, 6 it may be preferable for the peptides to have a higher k off value because the catalyst requires prompt release from the antibody after the reaction to interact with another target molecule, resulting in an enhanced catalytic cycle. IgG-binding peptides appropriate for preparing the immune-liposome, 16 noncovalent-type ADC, 17 or half-life extension conjugate 18 are better if they have a slow dissociation rate, that is, a low k off value that leads to the suppression of their undesired dissociation from antibodies in circulating blood.…”

Section: Introductionmentioning

confidence: 99%

Kinetics-Based Structural Requirements of Human Immunoglobulin G Binding Peptides

et al. 2019

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Currently, antibodies are widely used not only in research but also in therapy. Hence, peptides that selectively bind to the fragment crystallizable site of an antibody have been extensively utilized in various research efforts such as the preparation of antibody–drug conjugates (ADC). Consequently, appropriate peptides that bind to immunoglobulin G (IgG) with a specific Kd value and also kon and koff values will be useful in different applications, and these kinetic parameters have been perhaps overlooked but are key to development of peptide ligands with advantageous binding properties. We prepared structural derivatives of IgG-binding peptide 1 and evaluated the binding affinity and kinetic rates of the products by surface plasmon resonance assay and isothermal titration calorimetry to obtain novel peptides with beneficial antibody binding properties. In this way, 15-Lys8Leu with fast-binding and slow-release features was obtained through a shortened peptide 15-IgBP. On the other hand, we successfully obtained distinctive peptide, 15-Lys8Tle, with a similar Kd value but with kon and koff values that were as much as six-fold different from those of 15-IgBP. These new peptides are useful for the elucidation of kinetic effects on the function of IgG-binding peptides and various applications of antibody or antibody–drug interactions, such as immunoliposome, ADC, or half-life extension strategy, by using a peptide with the appropriate kinetic features.

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“…Conjugation of the peptide to a dye or MRI contrast agent could be used for in vivo (tumor) imaging in patients undergoing antibody treatment. Non-covalent antibody conjugates have been explored by several groups (41)(42)(43), mostly making use of generic Fc-binding protein domains (e.g. Staphylococcus aureus protein A).…”

Section: Discussionmentioning

confidence: 99%

Affinity Maturation of a Cyclic Peptide Handle for Therapeutic Antibodies Using Deep Mutational Scanning

Rosmalen

Janssen

Hendrikse

et al. 2017

Journal of Biological Chemistry

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Edited by Luke O'NeillMeditopes are cyclic peptides that bind in a specific pocket in the antigen-binding fragment of a therapeutic antibody such as cetuximab. Provided their moderate affinity can be enhanced, meditope peptides could be used as specific non-covalent and paratope-independent handles in targeted drug delivery, molecular imaging, and therapeutic drug monitoring. Here we show that the affinity of a recently reported meditope for cetuximab can be substantially enhanced using a combination of yeast display and deep mutational scanning. Deep sequencing was used to construct a fitness landscape of this protein-peptide interaction, and four mutations were identified that together improved the affinity for cetuximab 10-fold to 15 nM. Importantly, the increased affinity translated into enhanced cetuximab-mediated recruitment to EGF receptor-overexpressing cancer cells. Although in silico Rosetta simulations correctly identified positions that were tolerant to mutation, modeling did not accurately predict the affinity-enhancing mutations. The experimental approach reported here should be generally applicable and could be used to develop meditope peptides with low nanomolar affinity for other therapeutic antibodies.

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Novel Hybrid Compound of a Plinabulin Prodrug with an IgG Binding Peptide for Generating a Tumor Selective Noncovalent-Type Antibody–Drug Conjugate

Cited by 23 publications

References 32 publications

Fc-Binding Ligands of Immunoglobulin G: An Overview of High Affinity Proteins and Peptides

Fc-Binding Ligands of Immunoglobulin G: An Overview of High Affinity Proteins and Peptides

Kinetics-Based Structural Requirements of Human Immunoglobulin G Binding Peptides

Affinity Maturation of a Cyclic Peptide Handle for Therapeutic Antibodies Using Deep Mutational Scanning

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