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Cambridge Biosciences DTP PhD Programme

 

Congratulations to Josie Gaynord, 2014 cohort PhD student in the BBSRC DTP Programme, for publishing the paper Two‐Component Stapling of Biologically Active and Conformationally Constrained Peptides: Past, Present, and Future’ in Advanced Therapeutics.

Abstract

Peptides are an emerging class of therapeutics in the pharmaceutical world. Whilst small molecules have dominated the therapeutic landscape for decades, the design and application of peptide drugs is emerging among the pharmaceutical industries and academia. Although highly selective and efficacious, peptides are characterized by poor pharmacokinetic properties and amelioration of their bioavailability remains a major hurdle. Incorporation of conformational constraints within the peptide (such as peptide stapling) has been extensively used to improve the bioavailability of these molecules; consequently, it is not surprising that a plethora of stapling techniques has been developed and has had a significant impact on the development of peptide therapeutics. Among the numerous stapling techniques known, two‐component methodologies allow facile and divergent functionalization of peptides. The authors have pioneered a stapling technique that makes use of the double Cu‐catalyzed azide–alkyne cycloaddition between di‐azido peptides and functionalized di‐alkynyl staples. In recent years, the authors have created biologically active, conformationally constrained peptides functionalized with cell‐penetrating peptides, fluorescent tags, and photo cross‐linking moieties, demonstrating the wide applicability of this methodology. Herein, the impact, advantages, limitations, and future applications of this technology and other two‐component peptide stapling techniques on the development of clinically relevant peptides are highlighted.

To read the full publication, please click here.

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