Rational design of an anticalin-type sugar-binding protein using a genetically encoded boronate side chain

Edwardraja, Selvakumar, Eichinger, Andreas, Theobald, Ina, Sommer, Carina Andrea, Reichert, Andreas J and Skerra, Arne (2017) Rational design of an anticalin-type sugar-binding protein using a genetically encoded boronate side chain. ACS Synthetic Biology, 6 12: 2241-2247. doi:10.1021/acssynbio.7b00199


Author Edwardraja, Selvakumar
Eichinger, Andreas
Theobald, Ina
Sommer, Carina Andrea
Reichert, Andreas J
Skerra, Arne
Title Rational design of an anticalin-type sugar-binding protein using a genetically encoded boronate side chain
Journal name ACS Synthetic Biology   Check publisher's open access policy
ISSN 2161-5063
Publication date 2017-09-22
Sub-type Article (original research)
DOI 10.1021/acssynbio.7b00199
Open Access Status Not yet assessed
Volume 6
Issue 12
Start page 2241
End page 2247
Total pages 7
Place of publication Washington, DC, United States
Publisher American Chemical Society
Language eng
Subject 2204 Biomedical Engineering
1301 Biochemistry, Genetics and Molecular Biology (miscellaneous)
Abstract The molecular recognition of carbohydrates plays a fundamental role in many biological processes. However, the development of carbohydrate-binding reagents for biomedical research and use poses a challenge due to the generally poor affinity of proteins toward sugars in aqueous solution. Here, we describe the effective molecular recognition of pyranose monosaccharides (in particular, galactose and mannose) by a rationally designed protein receptor based on the human lipocalin scaffold (Anticalin). Complexation relies on reversible covalent cis-diol boronate diester formation with a genetically encoded l-boronophenylalanine (Bpa) residue which was incorporated as a non-natural amino acid at a sterically permissive position in the ligand pocket of the Anticalin, as confirmed by X-ray crystallography. Compared with the metal-ion and/or avidity-dependent oligovalent lectins that prevail in nature, our approach offers a novel and promising route to generate tight sugar-binding reagents both as research reagents and for biomedical applications.
Keyword Amber suppression
Borocalin
Boronophenylalanine
Carbohydrate recognition
Non-natural amino acid
Protein design
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID ALTF 858-2011
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Institute for Molecular Bioscience - Publications
 
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Created: Wed, 15 Nov 2017, 13:51:31 EST