Premium
Programming A Molecular Relay for Ultrasensitive Biodetection through 129 Xe NMR
Author(s) -
Wang Yanfei,
Roose Benjamin W.,
Philbin John P.,
Doman Jordan L.,
Dmochowski Ivan J.
Publication year - 2016
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201508990
Subject(s) - chemistry , supramolecular chemistry , carbonic anhydrase ii , nuclear magnetic resonance spectroscopy , crystallography , stereochemistry , carbonic anhydrase , biochemistry , enzyme , crystal structure
A supramolecular strategy for detecting specific proteins in complex media by using hyperpolarized 129 Xe NMR is reported. A cucurbit[6]uril (CB[6])‐based molecular relay was programmed for three sequential equilibrium conditions by designing a two‐faced guest (TFG) that initially binds CB[6] and blocks the CB[6]–Xe interaction. The protein analyte recruits the TFG and frees CB[6] for Xe binding. TFGs containing CB[6]‐ and carbonic anhydrase II (CAII)‐binding domains were synthesized in one or two steps. X‐ray crystallography confirmed TFG binding to Zn 2+ in the deep CAII active‐site cleft, which precludes simultaneous CB[6] binding. The molecular relay was reprogrammed to detect avidin by using a different TFG. Finally, Xe binding by CB[6] was detected in buffer and in E. coli cultures expressing CAII through ultrasensitive 129 Xe NMR spectroscopy.