TY - JOUR
T1 - Single-molecule spectroscopy of amino acids and peptides by recognition tunnelling
AU - Zhao, Yanan
AU - Ashcroft, Brian
AU - Zhang, Peiming
AU - Liu, Hao
AU - Sen, Suman
AU - Song, Weisi
AU - Im, Jongone
AU - Gyarfas, Brett
AU - Manna, Saikat
AU - Biswas, Sovan
AU - Borges, Chad
AU - Lindsay, Stuart
N1 - Funding Information:
S. Chang assisted in the original survey of amino acids. The authors thank P. Pang, P. Krstic, C. Hernandez-Suarez and W. Offenberg for useful discussions. This work was supported in part by a DNA sequencing technology grant from the NHGRI (HG 006323).
PY - 2014/6
Y1 - 2014/6
N2 - The human proteome has millions of protein variants due to alternative RNA splicing and post-translational modifications, and variants that are related to diseases are frequently present in minute concentrations. For DNA and RNA, low concentrations can be amplified using the polymerase chain reaction, but there is no such reaction for proteins. Therefore, the development of single-molecule protein sequencing is a critical step in the search for protein biomarkers. Here, we show that single amino acids can be identified by trapping the molecules between two electrodes that are coated with a layer of recognition molecules, then measuring the electron tunnelling current across the junction. A given molecule can bind in more than one way in the junction, and we therefore use a machine-learning algorithm to distinguish between the sets of electronic a €fingerprintsa € associated with each binding motif. With this recognition tunnelling technique, we are able to identify D and L enantiomers, a methylated amino acid, isobaric isomers and short peptides. The results suggest that direct electronic sequencing of single proteins could be possible by sequentially measuring the products of processive exopeptidase digestion, or by using a molecular motor to pull proteins through a tunnel junction integrated with a nanopore.
AB - The human proteome has millions of protein variants due to alternative RNA splicing and post-translational modifications, and variants that are related to diseases are frequently present in minute concentrations. For DNA and RNA, low concentrations can be amplified using the polymerase chain reaction, but there is no such reaction for proteins. Therefore, the development of single-molecule protein sequencing is a critical step in the search for protein biomarkers. Here, we show that single amino acids can be identified by trapping the molecules between two electrodes that are coated with a layer of recognition molecules, then measuring the electron tunnelling current across the junction. A given molecule can bind in more than one way in the junction, and we therefore use a machine-learning algorithm to distinguish between the sets of electronic a €fingerprintsa € associated with each binding motif. With this recognition tunnelling technique, we are able to identify D and L enantiomers, a methylated amino acid, isobaric isomers and short peptides. The results suggest that direct electronic sequencing of single proteins could be possible by sequentially measuring the products of processive exopeptidase digestion, or by using a molecular motor to pull proteins through a tunnel junction integrated with a nanopore.
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U2 - 10.1038/nnano.2014.54
DO - 10.1038/nnano.2014.54
M3 - Article
C2 - 24705512
AN - SCOPUS:84902295162
SN - 1748-3387
VL - 9
SP - 466
EP - 473
JO - Nature nanotechnology
JF - Nature nanotechnology
IS - 6
ER -