Versatile protein recognition by the encoded display of multiple chemical elements on a constant macrocyclic scaffold.

Abstract

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.

• Authors: Yizhou Li, Roberto De Luca, Samuele Cazzamalli, Francesca Pretto, Davor Bajic, Jörg Scheuermann, Dario Neri
• Journal: Nature chemistry (Nat Chem) Vol. 10 Issue 4 Pg. 441-448 (04 2018) ISSN: 1755-4349 [Electronic] England
• PMID: 29556050 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Calmodulin
• Macrocyclic Compounds
• Orosomucoid
• Tumor Necrosis Factor-alpha
• Horseradish Peroxidase
• Tankyrases
• TNKS protein, human
• Prostate-Specific Antigen
• Carbonic Anhydrase IX
• Serum Albumin, Human

Topics

• Calmodulin (analysis)
• Carbonic Anhydrase IX (analysis, metabolism)
• Horseradish Peroxidase (analysis, metabolism)
• Humans
• Macrocyclic Compounds (chemistry)
• Microscopy, Fluorescence
• Orosomucoid (analysis)
• Prostate-Specific Antigen (analysis)
• Serum Albumin, Human (analysis)
• Tankyrases (analysis, metabolism)
• Tumor Necrosis Factor-alpha (analysis)