Advancing the careers of life science professionals of Indian origin

Junutula, Jagath R.; Raman, Praveena; Patel, Darshana; Butler, H. N.; Jayasuriya, A

doi:10.1038/nbt0710-757

Cited by 1 publication

(2 citation statements)

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“…Most site‐specific conjugation techniques developed for mAbs are genetic modification methods, which aim to introduce unnatural amino acids to incorporate a bioorthogonal functional group or free cysteine residue into an antibody. Enzymatic conjugation strategies, such as transglutaminase‐driven glutamine modification and glycan remodelling, have also been tested.…”

Section: Figurementioning

confidence: 99%

“…Having established a reliable conjugation route, we then carefully planned and executed the synthesis of an ADC from an AAPC 1 (Figure a). THIOMAB is a well‐defined technology that is used in antibody engineering to introduce a reactive cysteine residue in a site‐specific manner. To expose the reactive cysteine residues, cleavage of inter‐chain (and engineered cysteine caps) disulphide bonds with a reducing agent is followed by a spontaneous re‐oxidation step to re‐connect the intermolecular disulfide bond between a heavy chain and a light chain (HC‐LC) and/or between the two heavy chains (HC‐HC).…”

Section: Figurementioning

confidence: 99%

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AJICAP: Affinity Peptide Mediated Regiodivergent Functionalization of Native Antibodies

et al. 2019

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The need for atom‐precise biomolecule modification, and particularly the irreversible formation of covalent bonds to specific amino acids in proteins, has become an essential issue in the fields of pharmaceuticals and chemical biology. For example, antibody–drug conjugates (ADCs) are increasingly common entries into the clinical oncology pipeline. Herein, we report a new method of affinity peptide mediated regiodivergent functionalization (AJICAP™) that enables the synthesis of ADCs from native IgG antibodies. We succeeded in introducing thiol functional groups onto three lysine residues in IgGs using Fc affinity peptide reagents without antibody engineering. A cytotoxic molecule was then connected to the newly introduced thiol group, and both a surface plasmon resonance binding assay and in vivo xenograft mouse model results showed that the resulting ADC could selectively target and kill HER2‐positive cells. Our strategy provides a new approach for constructing complex antibody‐derived biomolecules.

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Section: Figurementioning

confidence: 99%

Section: Figurementioning

confidence: 99%