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, . 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 2017-10-18
Sub-type Article (original research)
DOI 10.1021/acssynbio.7b00199
Open Access Status Not yet assessed
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
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: Pubmed Import
 
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Created: Wed, 15 Nov 2017, 13:51:31 EST