Universität zu Köln

Walpurgis, Katja, Thomas, Andreas and Thevis, Mario (2019). Detection of the myostatin-neutralizing antibody Domagrozumab in serum by means of Western blotting and LC-HRMS. Drug Test. Anal., 11 (11-12). S. 1714 - 1724. HOBOKEN: WILEY. ISSN 1942-7611

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Abstract

The TGF-beta cytokine myostatin is considered to be one of the key regulators of skeletal muscle mass. Consequently, specific inhibitors of the growth factor and its signaling pathways are promising therapeutics for the treatment of muscle wasting disorders as well as potential performance-enhancing agents in sports. Domagrozumab is a humanized monoclonal antibody that neutralizes the circulating cytokine, thus preventing receptor activation. Within this study, two complementary detection assays for Domagrozumab from serum were developed by using ammonium sulfate precipitation and immunoaffinity purification either in combination with tryptic digestion and LC-HRMS or Western blotting. While the LC-HRMS assay is highly specific for diagnostic peptides originating from both the heavy and the light chain of the antibody, the second assay is capable of generically detecting intact therapeutic proteins comprising a human Fc domain and exhibiting high specificity for dimeric myostatin/GDF-11. Following optimization, both assays were comprehensively characterized. They can readily be modified to include further protein drugs and will expand the range of available tests for emerging myostatin inhibitors.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Walpurgis, Katja UNSPECIFIED UNSPECIFIED UNSPECIFIED Thomas, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Thevis, Mario UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-128588
DOI:	10.1002/dta.2729
Journal or Publication Title:	Drug Test. Anal.
Volume:	11
Number:	11-12
Page Range:	S. 1714 - 1724
Date:	2019
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1942-7611
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MUSCLE HYPERTROPHY; MUTATION; PERFORMANCE; REGULATOR; PEPTIDES; MASS Multiple languages Biochemical Research Methods; Chemistry, Analytical; Pharmacology & Pharmacy Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/12858