ABSTRACT

Introduction

Anticalin proteins are engineered versions of lipocalins that constitute a novel class of clinical-stage biopharmaceuticals. The lipocalins exhibit a central β-barrel with eight antiparallel β-strands and an α-helix attached to its side. Four structurally variable loops at the open end of the β-barrel form a pronounced binding pocket, which can be reshaped to generate specificities toward diverse disease-relevant molecular targets.

Areas covered

This 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 opinion

Combinatorial 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•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.

中文翻译：

---

Anticalin® 蛋白质：从工作台到床边

摘要

介绍

Anticalin 蛋白是脂质运载蛋白的工程版本，构成一类新型的临床阶段生物药物。脂质运载蛋白表现出一个中央 β 桶，带有 8 条反平行的 β 链和一个连接在其侧面的 α 螺旋。β-桶开口端的四个结构可变环形成一个明显的结合袋，可以对其进行重塑以产生针对不同疾病相关分子靶标的特异性。

覆盖区域

本文回顾了 Anticalin 工程的现状，从基本原理到通过组合蛋白质设计和定向进化开发具有高靶点亲和力和特异性的 Anticalin，包括临床前和临床开发中基于 Anticalin 的候选药物的示例。

专家意见

组合基因文库与强大的分子选择技术相结合，使脂质运载蛋白的天然配体特异性从小分子扩展到肽和蛋白质。这一生物分子概念已通过一系列 Anticalin•target 复合物的结构分析得到验证。在（免疫）肿瘤学、代谢和呼吸系统疾病领域，作为治疗中毒的解毒剂和新型抗生素，有希望的 Anticalin 主要候选药物已达到不同的临床前和临床开发阶段。因此，Anticalins 提供了一种替代抗体的替代品，具有作为下一代生物制剂的有前途和潜在的优越特性。