Chemical Epitope Targeting: Review of a Novel Screening Technology

Ul-Ain, Qurrat; Kandler, Rene; Gillespie, Dylan; Nag, Arundhati

doi:10.16966/2578-9589.110

J Med Chem Drug Des

2018

DOI: 10.16966/2578-9589.110

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Chemical Epitope Targeting: Review of a Novel Screening Technology

Qurrat Ul-Ain¹,

Rene Kandler²,

Dylan Gillespie³

et al.

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Protein-Catalyzed Capture Agents

Agnew¹,

Coppock

Idso

et al. 2019

Chem. Rev.

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Protein-catalyzed capture agents (PCCs) are synthetic and modular peptide-based affinity agents that are developed through the use of single generation in situ click chemistry screens against large peptide libraries. In such screens, the target protein, or a synthetic epitope fragment of that protein, provides a template for selectively promoting the non-copper catalyzed azide-alkyne dipolar cycloaddition click reaction between either a library peptide and a known ligand, or a library peptide and the synthetic epitope. The development of epitope-targeted PCCs was motivated by the desire to fully generalize pioneering work from the Sharpless and Finn groups in which in situ click screens were used to develop potent, divalent enzymatic inhibitors. In fact, a large degree of generality has now been achieved. Various PCCs have demonstrated utility for selective protein detection, as allosteric or direct inhibitors, as modulators of protein folding, and as tools for in vivo tumor imaging. We provide a historical context for PCCs, and place them within the broader scope of biological and synthetic aptamers. The development of PCCs is presented as: (i) Generation I PCCs, which are branched ligands engineered through an iterative, non-epitope targeted process, and (ii) Generation II PCCs, which are typically developed from macrocyclic peptide libraries and are precisely epitope targeted. We provide statistical comparisons of Generation II PCCs relative to monoclonal antibodies in which the protein target is the same. Finally, we discuss current challenges and future opportunities of PCCs.

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Protein-Catalyzed Capture Agents

Agnew¹,

Coppock

Idso

et al. 2019

Chem. Rev.

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Biological applications of amide and amino acid containing synthetic macrocycles

Borges

Gillespie

Nag

2019

Supramolecular Chemistry

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Chemical Epitope Targeting: Review of a Novel Screening Technology

Cited by 2 publications

References 0 publications

Protein-Catalyzed Capture Agents

Protein-Catalyzed Capture Agents

Biological applications of amide and amino acid containing synthetic macrocycles

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