US EPA

7056160 

Journal Article 

Anticalin (R) proteins: from bench to bedside 

Deuschle, FC; Ilyukhina, E; Skerra, A; , 

2020 

Yes 

Expert Opinion on Biological Therapy
ISSN: 1471-2598 

TAYLOR & FRANCIS LTD 

ABINGDON 

33074019 

10.1080/14712598.2021.1839046 

WOS:000583438500001 

IntroductionAnticalin proteins are engineered versions of lipocalins that constitute a novel class of clinical-stage biopharmaceuticals. The lipocalins exhibit a central beta-barrel with eight antiparallel beta-strands and an alpha-helix attached to its side. Four structurally variable loops at the open end of the beta-barrel form a pronounced binding pocket, which can be reshaped to generate specificities toward diverse disease-relevant molecular targets.Areas coveredThis article reviews the current status of Anticalin engineering, from the basic principles to the development of Anticalins with high target affinity and specificity via combinatorial protein design and directed evolution, including examples of Anticalin-based drug candidates under preclinical and clinical development.Expert opinionCombinatorial gene libraries together with powerful molecular selection techniques have enabled the expansion of the natural ligand specificities of lipocalins from small molecules to peptides and proteins. This biomolecular concept has been validated by structural analyses of a series of Anticalin center dot target complexes. Promising Anticalin lead candidates have reached different preclinical and clinical development stages in the areas of (immuno)oncology, metabolic, and respiratory diseases, as antidotes to treat intoxications and as novel antibiotics. Thus, Anticalins offer an alternative to antibodies with promising and potentially superior features as next-generation biologics.