Rational design of humanized antibody inhibitors for cathepsin S

Yu, Po-Wen; Kao, Guoyun; Dai, Zhefu; Nasertorabi, Fariborz; Zhang, Yong

doi:10.1016/j.abb.2023.109849

Archives of Biochemistry and Biophysics

2024

DOI: 10.1016/j.abb.2023.109849

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Rational design of humanized antibody inhibitors for cathepsin S

Po-Wen Yu,

Guoyun Kao,

Zhefu Dai

et al.

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2024

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Cited by 2 publications

References 52 publications

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Synthesis of site‐specific Fab‐drug conjugates using ADP‐ribosyl cyclases

Kim,

Hariri,

Zhang

et al. 2024

Protein Science

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Targeted delivery of small‐molecule drugs via covalent attachments to monoclonal antibodies has proved successful in clinic. For this purpose, full‐length antibodies are mainly used as drug‐carrying vehicles. Despite their flexible conjugation sites and versatile biological activities, intact immunoglobulins with conjugated drugs, which feature relatively large molecular weights, tend to have restricted tissue distribution and penetration and low fractions of payloads. Linking small‐molecule therapeutics to other formats of antibody may lead to conjugates with optimal properties. Here, we designed and synthesized ADP‐ribosyl cyclase‐enabled fragment antigen‐binding (Fab) drug conjugates (ARC‐FDCs) by utilizing CD38 catalytic activity. Through rapidly forming a stable covalent bond with a nicotinamide adenine dinucleotide (NAD+)‐based drug linker at its active site, CD38 genetically fused with Fab mediates robust site‐specific drug conjugations via enzymatic reactions. Generated ARC‐FDCs with defined drug‐to‐Fab ratios display potent and antigen‐dependent cytotoxicity against breast cancer cells. This work demonstrates a new strategy for developing site‐specific FDCs. It may be applicable to different antibody scaffolds for therapeutic conjugations, leading to novel targeted agents.

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Synthesis of site‐specific Fab‐drug conjugates using ADP‐ribosyl cyclases

Kim,

Hariri,

Zhang

et al. 2024

Protein Science

Self Cite

View full text Add to dashboard Cite

show abstract

Functional analysis of novel cystatins from Haemaphysalis doenitzi and evaluation of their roles in cypermethrin and λ-cyhalothrin resistance

Zhang,

Gao,

Dong

et al. 2024

Pesticide Biochemistry and Physiology

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Rational design of humanized antibody inhibitors for cathepsin S

Cited by 2 publications

References 52 publications

Synthesis of site‐specific Fab‐drug conjugates using ADP‐ribosyl cyclases

Synthesis of site‐specific Fab‐drug conjugates using ADP‐ribosyl cyclases

Functional analysis of novel cystatins from Haemaphysalis doenitzi and evaluation of their roles in cypermethrin and λ-cyhalothrin resistance

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