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Title: Structural determination of intact proteins using mass spectrometry

Patent ·
OSTI ID:936326

The present invention relates to novel methods of determining the sequence and structure of proteins. Specifically, the present invention allows for the analysis of intact proteins within a mass spectrometer. Therefore, preparatory separations need not be performed prior to introducing a protein sample into the mass spectrometer. Also disclosed herein are new instrumental developments for enhancing the signal from the desired modified proteins, methods for producing controlled protein fragments in the mass spectrometer, eliminating complex microseparations, and protein preparatory chemical steps necessary for cross-linking based protein structure determination.Additionally, the preferred method of the present invention involves the determination of protein structures utilizing a top-down analysis of protein structures to search for covalent modifications. In the preferred method, intact proteins are ionized and fragmented within the mass spectrometer.

Research Organization:
Sandia National Lab. (SNL-CA), Livermore, CA (United States)
Sponsoring Organization:
USDOE
DOE Contract Number:
AC04-94AL85000
Assignee:
Sandia National Laboratories (Livermore, CA)
Patent Number(s):
7,368,290
Application Number:
10/437,268
OSTI ID:
936326
Country of Publication:
United States
Language:
English

References (7)

A top down approach to protein structural studies using chemical cross-linking and Fourier transform mass spectrometry journal January 2003
?Top down? protein characterization via tandem mass spectrometry journal January 2002
Protein mass spectrometry: applications to analytical biotechnology journal June 1995
High throughput protein fold identification by using experimental constraints derived from intramolecular cross-links and mass spectrometry journal May 2000
Top Down versus Bottom Up Protein Characterization by Tandem High-Resolution Mass Spectrometry journal February 1999
Structure and Assembly of the Catalytic Region of Human Complement Protease C1̄r:  A Three-Dimensional Model Based on Chemical Cross-Linking and Homology Modeling journal May 1997
Constrained walks and self-avoiding walks: implications for protein structure determination journal December 2001

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