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Advances in analysis of novel protei...

Northeastern University.

Advances in analysis of novel protein therapeutics and clinical samples with LC-MS/MS methods.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Advances in analysis of novel protein therapeutics and clinical samples with LC-MS/MS methods.
Author:	Yan, Fangfei.
Description:	206 p.
Notes:	Source: Dissertation Abstracts International, Volume: 74-08(E), Section: B.
Notes:	Adviser: William S. Hancock.
Contained By:	Dissertation Abstracts International74-08B(E).
Subject:	Chemistry, Analytical.
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3558797
ISBN:	9781303033803

Advances in analysis of novel protein therapeutics and clinical samples with LC-MS/MS methods.
Yan, Fangfei.

Advances in analysis of novel protein therapeutics and clinical samples with LC-MS/MS methods. - 206 p.

Source: Dissertation Abstracts International, Volume: 74-08(E), Section: B.

Thesis (Ph.D.)--Northeastern University, 2013.

Analytical characterization is essential for drug efficacy, stability and safety. Significant concern in protein stability and potential immunogenicity requires detailed characterization of protein therapeutics. Therefore, the ability to detect product variants from non-clonal cell lines is very important. To fulfill this job, LC-MS/MS becomes the perfect choice. This Ph.D. research discusses advances in analysis of novel protein therapeutics and clinical samples with LC-MS/MS methods. Recombinant protein therapeutics is a major focus of my research work. In Chapter 1, an overview of production of recombinant protein therapeutics and the potential heterogeneity, in particular post-translational modifications, is reviewed. Common techniques for protein characterization are discussed, including electrophoresis, chromatography, and mass spectrometry. Because the major focus of my research is about mass spectrometry, further details about ionization method, mass analyzer, hybrid mass spectrometer, fragmentation method and LC-MS/MS analysis are reviewed. In addition, common strategies for protein characterization are discussed. Furthermore, biology part for proteomic analysis is reviewed. ERBB2, an important oncogene, is of particular interest and its association to cancer disease is included.

ISBN: 9781303033803Subjects--Topical Terms:

224793
Chemistry, Analytical.

Advances in analysis of novel protein therapeutics and clinical samples with LC-MS/MS methods.
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100 1 $a Yan, Fangfei. $3 660273
245 1 0 $a Advances in analysis of novel protein therapeutics and clinical samples with LC-MS/MS methods.
300 $a 206 p.
500 $a Source: Dissertation Abstracts International, Volume: 74-08(E), Section: B.
500 $a Adviser: William S. Hancock.
502 $a Thesis (Ph.D.)--Northeastern University, 2013.
520 $a Analytical characterization is essential for drug efficacy, stability and safety. Significant concern in protein stability and potential immunogenicity requires detailed characterization of protein therapeutics. Therefore, the ability to detect product variants from non-clonal cell lines is very important. To fulfill this job, LC-MS/MS becomes the perfect choice. This Ph.D. research discusses advances in analysis of novel protein therapeutics and clinical samples with LC-MS/MS methods. Recombinant protein therapeutics is a major focus of my research work. In Chapter 1, an overview of production of recombinant protein therapeutics and the potential heterogeneity, in particular post-translational modifications, is reviewed. Common techniques for protein characterization are discussed, including electrophoresis, chromatography, and mass spectrometry. Because the major focus of my research is about mass spectrometry, further details about ionization method, mass analyzer, hybrid mass spectrometer, fragmentation method and LC-MS/MS analysis are reviewed. In addition, common strategies for protein characterization are discussed. Furthermore, biology part for proteomic analysis is reviewed. ERBB2, an important oncogene, is of particular interest and its association to cancer disease is included.
520 $a Chapter 2, 3 and 4 detail my research projects. Chapter 2 is comprehensive mass spectrometric characterization of recombinant phenylalanine ammonia lyase (rAvPAL). Full characterization with the identification of the active site for this protein is discussed. Active sites of Rt PAL and GFP with similar structure were analyzed. The characterization process and strategies developed here are applied in the work of Chapter 3. Chapter 3 discusses the characterization of disulfide bond linkage and improper disulfide bridging of a variant of acidic lysosomal glucosidase (GAA) by LC-MS/MS. Here, details about the disulfide bond linkage analysis with the technique that ETD (electron transfer dissociation) is in combination with CID (collision induced dissociation) for fragmentation are included. The work flow including gel-based protein separation, enzymatic digestion and LC-MS/MS analysis were then applied in proteomic studies in Chapter 4. In Chapter 4, proteomic and genomic analysis of gastric cancer patient tissues is the topic. This includes proteomic studies with the help of LC-MS/MS. Also, the study of gastric cancer is part of the C-HPP Initiative, the exploration of proteomics and transcriptomics has provided in-depth analysis in oncology.
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650 4 $a Chemistry, Analytical. $3 224793
650 4 $a Chemistry, General. $3 226910
650 4 $a Chemistry, Biochemistry. $3 226900
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710 2 $a Northeastern University. $b Chemistry & Chemical Biology. $3 660274
773 0 $t Dissertation Abstracts International $g 74-08B(E).
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791 $a Ph.D.
792 $a 2013
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3558797

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