In nature, specific antibodies can be generated as a result of an adaptive selection and expansion of lymphocytes with suitable protein binding properties. We attempted to mimic antibody–antigen recognition by displaying multiple chemical diversity elements on a defined macrocyclic scaffold. Encoding of the displayed combinations was achieved using distinctive DNA tags, resulting in a library size of 35,393,112. Specific binders could be isolated against a variety of proteins, including carbonic anhydrase IX, horseradish peroxidase, tankyrase 1, human serum albumin, alpha-1 acid glycoprotein, calmodulin, prostate-specific antigen and tumour necrosis factor. Similar to antibodies, the encoded display of multiple chemical elements on a constant scaffold enabled practical applications, such as fluorescence microscopy procedures or the selective in vivo delivery of payloads to tumours. Furthermore, the versatile structure of the scaffold facilitated the generation of protein-specific chemical probes, as illustrated by photo-crosslinking.

在自然界中，通过适应性选择和扩增具有合适蛋白质结合特性的淋巴细胞，可以产生特异性抗体。我们试图通过在定义的大环支架上展示多种化学多样性元素来模拟抗体-抗原识别。显示组合的编码是使用独特的 DNA 标签实现的，导致文库大小为 35,393,112。可以分离针对多种蛋白质的特异性结合剂，包括碳酸酐酶 IX、辣根过氧化物酶、tankyrase 1、人血清白蛋白、α-1 酸性糖蛋白、钙调蛋白、前列腺特异性抗原和肿瘤坏死因子。与抗体类似，多种化学元素在恒定支架上的编码展示使实际应用成为可能，例如荧光显微镜程序或有效载荷的选择性体内递送至肿瘤。此外，支架的多功能结构促进了蛋白质特异性化学探针的产生，如光交联所示。