Universität zu Köln

Vogel, Matthias, Thomas, Andreas ORCID: 0000-0003-1199-0743, Schaenzer, Wilhelm and Thevis, Mario (2015). EPOR-Based Purification and Analysis of Erythropoietin Mimetic Peptides from Human Urine by Cys-Specific Cleavage and LC/MS/MS. J. Am. Soc. Mass Spectrom., 26 (9). S. 1617 - 1626. NEW YORK: SPRINGER. ISSN 1879-1123

Full text not available from this repository.

Abstract

The development of a new class of erythropoietin mimetic agents (EMA) for treating anemic conditions has been initiated with the discovery of oligopeptides capable of dimerizing the erythropoietin (EPO) receptor and thus stimulating erythropoiesis. The most promising amino acid sequences have been mounted on various different polymeric structures or carrier molecules to obtain highly active EPO-like drugs exhibiting beneficial and desirable pharmacokinetic profiles. Concomitant with creating new therapeutic options, erythropoietin mimetic peptide (EMP)-based drug candidates represent means to artificially enhance endurance performance and necessitate coverage by sports drug testing methods. Therefore, the aim of the present study was to develop a strategy for the comprehensive detection of EMPs in doping controls, which can be used complementary to existing protocols. Three model EMPs were used to provide proof-of-concept data. Following EPO receptor-facilitated purification of target analytes from human urine, the common presence of the cysteine-flanked core structure of EMPs was exploited to generate diagnostic peptides with the aid of a nonenzymatic cleavage procedure. Sensitive detection was accomplished by targeted-SIM/data-dependent MS2 analysis. Method characterization was conducted for the EMP-based drug peginesatide concerning specificity, linearity, precision, recovery, stability, ion suppression/enhancement, and limit of detection (LOD, 0.25 ng/mL). Additionally, first data for the identification of the erythropoietin mimetic peptides EMP1 and BB68 were generated, demonstrating the multi-analyte testing capability of the presented approach.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Vogel, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Thomas, Andreas UNSPECIFIED orcid.org/0000-0003-1199-0743 UNSPECIFIED Schaenzer, Wilhelm UNSPECIFIED UNSPECIFIED UNSPECIFIED Thevis, Mario UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-395939
DOI:	10.1007/s13361-015-1189-8
Journal or Publication Title:	J. Am. Soc. Mass Spectrom.
Volume:	26
Number:	9
Page Range:	S. 1617 - 1626
Date:	2015
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1879-1123
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MASS-SPECTROMETRIC DETECTION; PROTEIN HORMONE; RECEPTOR; PHARMACODYNAMICS; THERAPEUTICS; PEGINESATIDE; TECHNOLOGY; RESIDUES; CYSTEINE; PHAGE Multiple languages Biochemical Research Methods; Chemistry, Analytical; Chemistry, Physical; Spectroscopy Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/39593