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Multiplexed Discrimination of Single Amino Acid Residues in Polypeptides in a Single SERS Hot Spot
Author(s) -
Huang JianAn,
Mousavi Mansoureh Z.,
Giovannini Giorgia,
Zhao Yingqi,
Hubarevich Aliaksandr,
Soler Miguel A.,
Rocchia Walter,
Garoli Denis,
De Angelis Francesco
Publication year - 2020
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202000489
Subject(s) - aromatic amino acids , chemistry , amino acid , molecule , hot spot (computer programming) , residue (chemistry) , biochemistry , organic chemistry , computer science , operating system
The SERS‐based detection of protein sequences with single‐residue sensitivity suffers from signal dominance of aromatic amino acid residues and backbones, impeding detection of non‐aromatic amino acid residues. Herein, we trap a gold nanoparticle in a plasmonic nanohole to generate a single SERS hot spot for single‐molecule detection of 2 similar polypeptides (vasopressin and oxytocin) and 10 distinct amino acids that constitute the 2 polypeptides. Significantly, both aromatic and non‐aromatic amino acids are detected and discriminated at the single‐molecule level either at individual amino acid molecules or within the polypeptide chains. Correlated with molecular dynamics simulations, our results suggest that the signal dominance due to large spatial occupancy of aromatic rings of the polypeptide sidechains on gold surfaces can be overcome by the high localization of the single hot spot. The superior spectral and spatial discriminative power of our approach can be applied to single‐protein analysis, fingerprinting, and sequencing.