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.
Versatile protein recognition by the encoded display of multiple chemical elements on a constant macrocyclic scaffold
Posted by
Dario Neri
on 12 09 2019
Related content
12 05 2022
< 1 minute
Coupling stabilizers open KV1-type potassium channels
ABSTRACT: The opening and closing of voltage-gated ion channels are regulated by voltage sensors...
13 12 2021
< 1 minute
Cheminfo Stories 2021 Virtual UGM Asia Pacific Edition: Design of new compounds from the available chemical space
In computational compound design workflows, the analysis of the available chemical space is an...
12 11 2021
< 1 minute
Responding to the Challenge Posed by the Generic Control of Substances
Drug monitoring organizations report that new psychoactive substances continue to emerge, posing...
12 10 2021
< 1 minute
Boost analytical experiments with phys-chem properties
Physicochemical properties have a fundamental impact on analytical experiment conditions,...