The present invention is a method for measuring the amount of at least one molecule in a biological sample, the method comprising a) combining the sample, or a derivative thereof, with one or more aptamers and allowing one or more molecules in the sample to bind to the aptamer(s); b) separating bound from unbound molecules; and c) quantifying the molecule(s) bound to the or each aptamer, wherein quantification of the bound molecule(s) is carried out by sequencing at least part of the or each aptamer. Uses of and products derived from the method are also contemplated.

Disclosed herein, inter alia, are multivalent nucleotide constructs and methods for making and using such constructs.

Provided herein are methods and systems for sequencing proteins. One or more methods disclosed herein may use linkers having an amino acid-reactive group and an additional reactive moiety that may be used to couple a polymerizable molecule. The linker may couple to a polymerizable molecule and an amino acid of a peptide and a capture moiety via the polymerizable molecule, followed by cleavage of the amino acid from the peptide. Further processing and analysis may be conducted using, for example, nanopores or nanogaps.

Provided herein are methods and systems for sequencing proteins. One or more methods disclosed herein may use linkers having an amino acid-reactive group and an additional reactive moiety that may be used to couple a polymerizable molecule. The linker may couple to a polymerizable molecule and an amino acid of a peptide and a capture moiety via the polymerizable molecule, followed by cleavage of the amino acid from the peptide. Further processing and analysis may be conducted using, for example, nanopores or nanogaps.

The present disclosure relates to systems and methods for analysis of proteins, more in particular to nanopore systems, devices and methods for single-molecule protein analysis and sequencing. Provided is a method for translocating a target protein through a nanopore, the nanopore being comprised in a membrane separating a fluidic chamber of a nanopore system into a cis side and a trans side, comprising: (a) allowing a protein translocase in solution to capture and form a complex with the target protein to be translocated; (b) contacting the translocase-target protein complex with the cis side of the nanopore and allowing for translocation of the target protein to the trans side; wherein the nanopore system has a cis to trans electro-osmotic force (EOF) resulting from a large net ionic current flow cis-to-trans relative to the total ionic current flow, so that the target protein is captured in the nanopore with on top of the nanopore the translocase controlling the translocation.

The present invention relates to the field of biochemistry, more particularly to proteomics, more particularly to protein sequencing, even more particularly to single molecule peptide sequencing. The invention discloses methods for single molecule protein sequencing and/or amino acid identification using cleavage inducing agents which are not specific for one particular amino acid, cleave polypeptides step by step from the N-terminus onwards and provide information on the identity of the cleaved amino acids based on the reaction kinetics.

Immunogenic compositions comprising one or more polypeptides, wherein the one or more polypeptides: is capable of binding to Major Histocompatibility Complex (MHC) class I, and is derived from one or more proteins of SARS-COV-2. Also provided include methods of treating and preventing diseases using the immunogenic compositions.

The present invention provides a method for controlling a speed of a polypeptide passing through a nanopore and use thereof in determining an amino acid sequence of a polypeptide. Specifically, the method comprises: conjugating a polynucleotide to the polypeptide to give a polynucleotide-polypeptide conjugate, and applying a voltage across the nanopore in the presence of a polynucleotide binding enzyme to move the conjugate through the nanopore. The polynucleotide binding enzyme controls the movement of the polynucleotide and thereby controls the movement of the conjugated polypeptide in the nanopore, thus controlling the speed of the polypeptide passing through the nanopore.

The disclosure provides methods and compositions that enable the characterization of analytes in a sample, including the identification of polypeptides having one or more post-translational modifications. In some embodiments, the disclosure provides methods of determining a concentration of an analyte in a sample based at least in part on a count of detected series of signal pulses. In some embodiments, the disclosure provides methods of determining one or more chemical characteristics of an analyte (e.g., a polypeptide). In some embodiments, the disclosure provides a method (e.g., a single-molecule method) comprising contacting a single polypeptide with one or more post-translational modification-specific (PTM-specific) affinity reagents; and identifying whether the single polypeptide comprises a post-translational modification (PTM) by determining a luminescence signature representative of the binding interaction(s) between the single polypeptide and the one or more PTM-specific affinity reagents.

Provided herein are compounds of Formula (I). Also provided herein are amino acid recognition molecules, and salts thereof, comprising at least one instance of Formula (II), and compositions thereof. Further provided herein are methods of sequencing a polypeptide using an amino acid recognition molecule, or salt thereof, comprising at least one instance of Formulae (II) or (IV).