Towards the next generation of biomedicines by site-selective conjugation

Hu, Qiying; Berti, Francesco; Adamo, Roberto

doi:10.1039/c4cs00388h

Cited by 143 publications

(91 citation statements)

References 248 publications

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“…In addition, heterogeneous ADCs require complex mixture analyses to warrant batch-to-batch consistency. Homogeneous ADCs, by contrast, have a defined DAR with distinct pharmacological properties and, ideally, no batch-to-batch variability (Agarwal and Bertozzi, 2015; Hu et al, 2016; Panowski et al, 2014). Site-specific conjugation technologies have facilitated the manufacturing of homogenous ADCs.…”

Section: Introductionmentioning

confidence: 99%

Stable and Potent Selenomab-Drug Conjugates

Nelson

Nair

et al. 2017

Cell Chemical Biology

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Summary Selenomabs are engineered monoclonal antibodies with one or more translationally incorporated selenocysteine residues. The unique reactivity of the selenol group of selenocysteine permits site-specific conjugation of drugs. Compared to other natural and unnatural amino acid and carbohydrate residues that have been used for the generation of site-specific antibody-drug conjugates, selenocysteine is particularly reactive, permitting fast, single-step, and efficient reactions under near physiological conditions. Using a tailored conjugation chemistry, we generated highly stable selenomab-drug conjugates and demonstrated their potency and selectivity in vitro and in vivo. These site-specific antibody-drug conjugates built on a selenocysteine interface revealed broad therapeutic utility in liquid and solid malignancy models.

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Section: Introductionmentioning

confidence: 99%

Stable and Potent Selenomab-Drug Conjugates

Nelson

Nair

et al. 2017

Cell Chemical Biology

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“…These include lysine, tyrosine, arginine, glutamate, aspartate, serine, threonine, methionine, histidine and tryptophan side-chains, as well as N-terminal amines or C-terminal carboxyls (Basle et al . 2010; Hu et al . 2016; Lin et al .…”

Section: Molecular Engineering Toolbox For Complex Biological Samplesmentioning

confidence: 99%

A molecular engineering toolbox for the structural biologist

Debelouchina

Muir

2017

Quart. Rev. Biophys.

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Exciting new technological developments have pushed the boundaries of structural biology, and have enabled studies of biological macromolecules and assemblies that would have been unthinkable not long ago. Yet, the enhanced capabilities of structural biologists to pry into the complex molecular world have also placed new demands on the abilities of protein engineers to reproduce this complexity into the test tube. With this challenge in mind, we review the contents of the modern molecular engineering toolbox that allow the manipulation of proteins in a site-specific and chemically well-defined fashion. Thus, we cover concepts related to the modification of cysteines and other natural amino acids, native chemical ligation, intein and sortase-based approaches, amber suppression, as well as chemical and enzymatic bio-conjugation strategies. We also describe how these tools can be used to aid methodology development in X-ray crystallography, nuclear magnetic resonance, cryo-electron microscopy and in the studies of dynamic interactions. It is our hope that this monograph will inspire structural biologists and protein engineers alike to apply these tools to novel systems, and to enhance and broaden their scope to meet the outstanding challenges in understanding the molecular basis of cellular processes and disease.

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“…Detailed considerations regarding the protein carrier, attachment design, and linker chemistry are described in several recent reviews [28,31–33]. …”

Section: Introductionmentioning

confidence: 99%

Engineering a new generation of carbohydrate-based vaccines

Weyant

Mills

DeLisa

2018

Current Opinion in Chemical Engineering

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Recent advances in chemical synthesis, conjugation chemistry, engineered biosynthesis, and formulation design have spawned a new generation of vaccines that incorporate carbohydrate antigens. By providing better immunity against a variety of pathogens or malignant cells and lowering the cost of production, these developments overcome many of the limitations associated with conventional vaccines involving polysaccharides. Moreover, the resulting vaccine candidates are shedding light on how the immune system responds to carbohydrates and providing mechanistic insight that can help guide future vaccine design. Here, we review recent engineering efforts to develop and manufacture carbohydrate-based vaccines that are efficacious, durable, and cost-effective.

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Towards the next generation of biomedicines by site-selective conjugation

Cited by 143 publications

References 248 publications

Stable and Potent Selenomab-Drug Conjugates

Stable and Potent Selenomab-Drug Conjugates

A molecular engineering toolbox for the structural biologist

Engineering a new generation of carbohydrate-based vaccines

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