Quality control reagents and methods

Patent metadata

Field	Value
Publication number	US-10247711-B2
Application number	US-201414180125-A
Country	US
Kind code	B2
Filing date	Feb 13, 2014
Priority date	Feb 13, 2013
Publication date	Apr 2, 2019
Grant date	Apr 2, 2019

Abstract

The present invention provides reagents for instrumentation quality control and methods of use thereof. In particular, sets of peptides or other molecules are provided for evaluating the performance of instruments with mass spectrometry (MS) and/or liquid chromatography (LC) functionalities.

First claim

The invention claimed is:

1. A peptide mixture comprising three or more distinct-mass versions of each of two or more distinct-sequence peptides, wherein two or more of the distinct-sequence peptides are selected from SEQ ID NOS: 1-6, and wherein two or more of the distinct-mass versions of each distinct-sequence peptide comprises one or more amino acids with above natural-abundance levels of one or more heavy isotopes.

2. The peptide mixture of claim 1 , wherein all of the distinct-mass versions of any of the distinct-sequence peptides are present at distinct concentrations.

3. The peptide mixture of claim 2 , wherein the distinct-mass versions of any of the distinct-sequence peptides are present at concentrations ranging from at least as low as 10 nM to at least as high at 1 μM.

4. The peptide mixture of claim 3 , wherein the distinct-mass versions of any of the distinct-sequence peptides are present at concentrations ranging from 1 nM (femtomoles per microliter) to 10 μM.

5. The peptide mixture of claim 1 , wherein the distinct-sequence peptides are separable by liquid chromatography based on their different hydrophobicities.

6. The peptide mixture of claim 1 , wherein the distinct-sequence peptides are separable by liquid chromatography based on their different charge, size, or hydrophilicity.

7. The peptide mixture of claim 1 , comprising 3-20 distinct-sequence peptides.

8. The peptide mixture of claim 7 , comprising 5-10 distinct-sequence peptides.

9. The peptide mixture of claim 1 , wherein the distinct-mass versions of any of the distinct-sequence peptides are differentiable by mass spectrometry.

10. The peptide mixture of claim 1 , wherein the distinct-mass versions of any of the distinct-sequence peptides are the result of different combinations of stable heavy isotope-labeled amino acids.

11. The peptide mixture of claim 10 , wherein each of the distinct-mass versions of any of the distinct-sequence peptides comprises a different number of uniformly stable isotope-labeled amino acids.

12. The peptide mixture of claim 1 , comprising 3-20 distinct-mass versions of each of the distinct-sequence peptides.

13. The peptide mixture of claim 12 , comprising 5-10 distinct-mass versions of each of the distinct-sequence peptides.

14. The peptide mixture of claim 1 , comprising three or more distinct mass versions of peptides of each of SEQ ID NOS: 1-6.

15. The peptide mixture of claim 1 , comprising six distinct-sequence peptides comprising SEQ ID NOS: 1-6.

16. The peptide mixture of claim 15 , comprising peptides selected from: V*T*S*GST*ST*SR* (SEQ ID NO: 1), V*T*SGST*ST*SR* (SEQ ID NO: 1), V*T*SGSTSTSR* (SEQ ID NO: 1), V*TSGSTSTSR* (SEQ ID NO: 1), VTSGSTSTSR* (SEQ ID NO: 1), L*A*SV*SV*SR* (SEQ ID NO: 2), L*ASV*SV*SR* (SEQ ID NO: 2), LASV*SV*SR* (SEQ ID NO: 2), LASVSV*SR* (SEQ ID NO: 2), LASVSVSR* (SEQ ID NO: 2), YV*YV*ADV*A*A*K* (SEQ ID NO: 3), YV*YV*ADV*AAK* (SEQ ID NO: 3), YVYV*ADV*AAK* (SEQ ID NO: 3), YVYVADV*AAK* (SEQ ID NO: 3), YVYVADVAAK* (SEQ ID NO: 3), V*V*GGL*V*ALR* (SEQ ID NO: 4), V*V*GGLV*ALR* (SEQ ID NO: 4), V*V*GGLVALR* (SEQ ID NO: 4), V*VGGLVALR* (SEQ ID NO: 4), VVGGLVALR* (SEQ ID NO: 4), L*L*SL*GAGEF*K* (SEQ ID NO: 5), L*L*SL*GAGEFK* (SEQ ID NO: 5), L*L*SLGAGEFK* (SEQ ID NO: 5), L*LSLGAGEFK* (SEQ ID NO: 5), LLSLGAGEFK* (SEQ ID NO: 5), L*GF*TDL*F*SK* (SEQ ID NO: 6), L*GFTDL*F*SK* (SEQ ID NO: 6), L*GFTDL*FSK* (SEQ ID NO: 6), L*GFTDLFSK* (SEQ ID NO: 6), and LGFTDLFSK* (SEQ ID NO: 6) wherein * following a residue indicates above natural-abundance levels of one or more heavy isotopes.

17. The peptide mixture of claim 1 , comprising peptides selected from: V*T*S*GST*ST*SR* (SEQ ID NO: 1), V*T*SGST*ST*SR* (SEQ ID NO: 1), V*T*SGSTSTSR* (SEQ ID NO: 1), V*TSGSTSTSR* (SEQ ID NO: 1), VTSGSTSTSR* (SEQ ID NO: 1), L*A*SV*SV*SR* (SEQ ID NO: 2), L*ASV*SV*SR* (SEQ ID NO: 2), LASV*SV*SR* (SEQ ID NO: 2), LASVSV*SR* (SEQ ID NO: 2), LASVSVSR* (SEQ ID NO: 2), YV*YV*ADV*A*A*K* (SEQ ID NO: 3), YV*YV*ADV*AAK* (SEQ ID NO: 3), YVYV*ADV*AAK* (SEQ ID NO: 3), YVYVADV*AAK* (SEQ ID NO: 3), YVYVADVAAK* (SEQ ID NO: 3), V*V*GGL*V*ALR* (SEQ ID NO: 4), V*V*GGLV*ALR* (SEQ ID NO: 4), V*V*GGLVALR* (SEQ ID NO: 4), V*VGGLVALR* (SEQ ID NO: 4), VVGGLVALR* (SEQ ID NO: 4), L*L*SL*GAGEF*K* (SEQ ID NO: 5), L*L*SL*GAGEFK* (SEQ ID NO: 5), L*L*SLGAGEFK* (SEQ ID NO: 5), L*LSLGAGEFK* (SEQ ID NO: 5), LLSLGAGEFK* (SEQ ID NO: 5), L*GF*TDL*F*SK* (SEQ ID NO: 6), L*GFTDL*F*SK* (SEQ ID NO: 6), L*GFTDL*FSK* (SEQ ID NO: 6), L*GFTDLFSK* (SEQ ID NO: 6), and LGFTDLFSK* (SEQ ID NO: 6) wherein * following a residue indicates above natural-abundance levels of one or more heavy isotopes.

18. The peptide mixture of claim 17 , comprising peptides comprising: V*T*S*GST*ST*SR* (SEQ ID NO: 1), V*T*SGST*ST*SR* (SEQ ID NO: 1), V*T*SGSTSTSR* (SEQ ID NO: 1), V*TSGSTSTSR* (SEQ ID NO: 1), VTSGSTSTSR* (SEQ ID NO: 1), L*A*SV*SV*SR* (SEQ ID NO: 2), L*ASV*SV*SR* (SEQ ID NO: 2), LASV*SV*SR* (SEQ ID NO: 2), LASVSV*SR* (SEQ ID NO: 2), LASVSVSR* (SEQ ID NO: 2), YV*YV*ADV*A*A*K* (SEQ ID NO: 3), YV*YV*ADV*AAK* (SEQ ID NO: 3), YVYV*ADV*AAK* (SEQ ID NO: 3), YVYVADV*AAK* (SEQ ID NO: 3), YVYVADVAAK* (SEQ ID NO: 3), V*V*GGL*V*ALR* (SEQ ID NO: 4), V*V*GGLV*ALR* (SEQ ID NO: 4), V*V*GGLVALR* (SEQ ID NO: 4), V*VGGLVALR* (SEQ ID NO: 4), VVGGLVALR* (SEQ ID NO: 4), L*L*SL*GAGEF*K* (SEQ ID NO: 5), L*L*SL*GAGEFK* (SEQ ID NO: 5), L*L*SLGAGEFK* (SEQ ID NO: 5), L*LSLGAGEFK* (SEQ ID NO: 5), LLSLGAGEFK* (SEQ ID NO: 5), L*GF*TDL*F*SK* (SEQ ID NO: 6), L*GFTDL*F*SK* (SEQ ID NO: 6), L*GFTDL*FSK* (SEQ ID NO: 6), L*GFTDLFSK* (SEQ ID NO: 6), and LGFTDLFSK* (SEQ ID NO: 6) wherein * following a residue indicates above natural-abundance levels of one or more heavy isotopes.

Assignees

• Promega Corp

Inventors

• Coon Joshua Jacques
• Rosenblatt Michael M
• Urh Marjeta

Classifications

• G01N30/8665 Primary

  for calibrating the measuring apparatus · CPC title

• G01N2030/047

  external · CPC title

• G01N2030/8831

  involving peptides or proteins · CPC title

• H01J49/0009

  Calibration of the apparatus · CPC title

• G01N2030/027

  Liquid chromatography · CPC title