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Publication Number
US-11360095-B2
Publication Date
2022-06-14
Expiration Date
Abstract
The present invention relates to a set of two or more mass labels, wherein each mass label comprises the formula: X-L-M-Re wherein X is a reporter moiety having an exact mass, L is a bond cleavable by collision in a mass spectrometer, M is a mass modifier, and Re is a) a reactive functionality for attaching the mass label to an analyte or b) the analyte, wherein each mass label in the set has an integer mass, wherein each mass label in the set has the same integer mass, and wherein the set comprises two or more subsets of mass labels, each subset comprising one, two or more mass labels, and wherein, when the subset comprises two or more mass labels, the exact mass of the reporter moiety X of each mass label in the subset is different from the exact mass of the reporter moiety X of the mass labels in the same subset and in all other subsets, and wherein each mass label is distinguishable by mass spectrometry.
Core Innovation
The invention provides cisobaric mass labels for peptide/protein quantification in which each mass label has an isotopically defined formula X–L–M–Re. The mass label includes a reporter moiety X with an exact mass, a collision-cleavable linker L, a mass modifier M, and a reactive/analyte group Re, and the set contains two or more mass labels that share the same integer mass while differing in reporter-moiety exact mass configurations.
A key feature is that the set comprises two or more subsets of mass labels, and within each subset the exact mass of the reporter moiety X of each mass label is different. The different reporter moiety exact masses are chosen such that each mass label is distinguishable by mass spectrometry, and the disclosure explains using millidalton differences to distinguish labels within subsets while retaining a common integer mass across the overall set.
The reporter moiety X includes one or more isotopically marked positions represented by * in which oxygen is 18O, carbon is 13C, nitrogen is 15N, or hydrogen is 2H, with one or more * being present. The disclosure also relates to isotopically related tag sets that are approximately isobaric and uniquely resolvable from other tag sets, including pseudo-isobaric arrays with isobaric/co-selectable peptides and integer-mass distinctness across sets.
Claims Coverage
Independent claim clm-00001 defines mass labels with isotopically defined reporter moiety X and the same integer mass, arranged into two or more subsets with differing exact reporter-moiety masses so that each mass label is distinguishable by mass spectrometry. The covered features center on isotopic composition, integer mass assignment, subset partitioning, and spectrometric distinguishability.
Isotopically defined reporter moiety set with integer masses
A set of two or more mass labels wherein each mass label has a formula including a reporter moiety X having an exact mass, where * represents that oxygen is 18O, carbon is 13C, nitrogen is 15N or hydrogen is 2H and one or more * are present, and wherein each mass label in the set has an integer mass.
Same integer mass across the set
Each mass label in the set has the same integer mass.
Subsets with different exact reporter-moiety masses for distinguishability
The set comprises two or more subsets of mass labels, each subset comprising one, two or more mass labels, wherein when the subset comprises two or more mass labels the exact mass of the reporter moiety X of each mass label in the subset is different from the exact mass of the reporter moiety X of the mass labels in the same subset and in all other subsets, and wherein each mass label is distinguishable by mass spectrometry.
Cross-set distinct integer masses in an array
In an array of mass label sets, the integer mass of each mass label of any one set is different from the integer mass of each mass label of every other set in the array.
The claimed subject matter centers on an integer-mass, isotopically defined reporter moiety X set partitioned into subsets in which exact reporter-moiety masses differ within and across subsets, such that every mass label is distinguishable by mass spectrometry, with array-level distinct integer masses also described.
Stated Advantages
Mass labels are distinguishable by mass spectrometry while maintaining the same integer mass.
Enables simultaneous multiplexing of tag sets using pseudo-isobaric arrays.
Provides mass labels that are uniquely resolvable from other tag sets.
Makes each mass label distinguishable by mass spectrometry.
Documented Applications
Peptide/protein quantification using cisobaric mass labels (tandem mass tags).
Simultaneous multiplexing using pseudo-isobaric arrays for Tag Set 3 (36-plex) and Tag Set 4 (25-plex).
Use of isobaric/co-selectable peptides in conjunction with uniquely resolvable pseudo-isobaric arrays.
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