AJICAP: Affinity Peptide Mediated Regiodivergent Functionalization of Native Antibodies

Yamada, Kei; Shikida, Natsuki; Shimbo, Kazutaka; Ito, Yuji; Khedri, Zahra; Matsuda, Yutaka; Mendelsohn, Brian A.

doi:10.1002/anie.201814215

Cited by 86 publications

(141 citation statements)

References 58 publications

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“…Site‐specific modification of peptides and proteins is required for the development of pharmaceutical conjugates, bioimaging and medical diagnostics reagents, and protein‐based materials . Chemical approaches have been important tools for modification of reactive side chains in canonical amino acid residues including Lys, Cys, Tyr, Trp, Arg, and Met . The N terminus is an attractive accessible site for specific chemical modification because it represents a unique, yet ubiquitous position in proteins.…”

Section: Figurementioning

confidence: 99%

Triazolecarbaldehyde Reagents for One‐Step N‐Terminal Protein Modification

et al. 2020

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Site-specific modification of peptides and proteins is ak ey aspect of protein engineering.W ed eveloped am ethod for modification of the Nterminus of proteins using 1H-1,2,3-triazole-4-carbaldehyde( TA4C) derivatives, which can be prepared in one step. The N-terminal specific labelingo fb ioactive peptides and proteins with the TA4C derivatives proceeds under mild reactionc onditions in excellent conversion (angiotensinI: 92 %, ribonuclease A: 90 %). This method enables site-specific conjugation of various functional molecules such as fluorophores,b iotin, and polyethylene glycol attached to the triazole ring to the Nterminus. Furthermore, af unctional molecule modified with ap rimary amine moiety can be directly converted into aT A4C derivativethrough aDimroth rearrangement reaction with 1-(4-nitrophenyl)-1H-1,2,3-triazole-4-carbaldehyde. This methodc an be used to obtain N-terminal-modifiedp roteins via only two steps:1 )convenient preparation of aT A4C derivativew ith af unctional group and 2) modification of the Nterminus of the protein with the TA4C derivative.

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Section: Figurementioning

confidence: 99%

Triazolecarbaldehyde Reagents for One‐Step N‐Terminal Protein Modification

et al. 2020

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“…A recent study showed that chemical coupling between a protein and a small molecule achieved site‐specificity by introducing a guiding moiety into the molecule to be modified . In fact, this technique is well‐established for site‐specific antibody–drug conjugate synthesis .…”

Section: Discussionmentioning

confidence: 99%

Synthetic Strategies for Artificial Lipidation of Functional Proteins

Takahara

Kamiya

2020

Chemistry A European J

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Biosynthesis of natural lipidated proteins is linked to important signal pathways, and therefore analyzing protein lipidation is crucial for understanding cellular functions. Artificial lipidation of proteins has attracted attention in recent decades as it allows modulation of the amphiphilic nature of the protein of interest, and is used in the design of drug‐delivery systems containing antibodies anchored on a lipid bilayer carrier. However, the intrinsic hydrophobicity of lipids makes the synthesis of lipid–protein conjugates challenging with respect to the yield and selectivity of the lipidation. In this Minireview, the development of chemical and enzymatic synthetic strategies for the preparation of a range of lipid–protein conjugates that do not compromise the functions of the proteins are discussed as well as applications of the conjugates.

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“…Further investigation was needed for the affinity‐peptide‐mediated labeling system, and Ohata and Ball and Yamada et al . reported a practical method for peptide traceless labeling for ADC development and immunoconjugate therapies.…”

Section: Affinity Peptide Labeling For Site‐specific Conjugation Of Nmentioning

confidence: 99%

Recent Chemical Approaches for Site‐Specific Conjugation of Native Antibodies: Technologies toward Next‐Generation Antibody–Drug Conjugates

Yamada

Ito

2019

ChemBioChem

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Antibody–drug conjugates (ADCs), which consist of three components, antibody, linker, and payload, can function as “magic bullets”. These conjugates offer the ability to target drug delivery to specific cells, based on cell‐specific recognition and the binding of an antigen by a monoclonal antibody (mAb). In particular, by delivering a cytotoxic payload to cancer cells, ADCs are expected to provide a breakthrough in oncology treatments by providing a way to increase efficacy and decrease toxicity, in comparison with traditional chemotherapeutic treatments. The development of ADC therapeutics has dramatically progressed in the past decade and two ADCs have been approved and used as anticancer drugs in the clinic. However, several critical issues regarding the performance of ADCs are still being discussed and investigated. Indeed, in the past few years, several groups have reported that, changing the number and position of the drug payloads in the ADCs, affects the pharmacokinetics, drug release rates, and biological activity. The use of conventional heterogeneous conjugation methods for ADC preparation results in the drug/antibody ratio and connecting position of the payload having stochastic distributions. Therefore, it is important to investigate how these potential problems can be circumvented through site‐specific conjugation. Herein, various site‐specific chemical conjugation strategies with native mAbs that are currently used for the production of ADCs, including residue‐selective labeling for generating ADCs, disulfide rebridging, and affinity‐peptide‐mediated site‐specific chemical conjugation technologies, are reviewed and described.

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AJICAP: Affinity Peptide Mediated Regiodivergent Functionalization of Native Antibodies

Cited by 86 publications

References 58 publications

Triazolecarbaldehyde Reagents for One‐Step N‐Terminal Protein Modification

Triazolecarbaldehyde Reagents for One‐Step N‐Terminal Protein Modification

Synthetic Strategies for Artificial Lipidation of Functional Proteins

Recent Chemical Approaches for Site‐Specific Conjugation of Native Antibodies: Technologies toward Next‐Generation Antibody–Drug Conjugates

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