Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Absence of the CXCR4 Antagonist EPI-X4 from Pharmaceutical Human Serum Albumin Preparations

Version 1 : Received: 9 March 2021 / Approved: 11 March 2021 / Online: 11 March 2021 (10:55:07 CET)

How to cite: Gilg, A.; Harms, M.; Olari, L.; Urbanowitz, A.; Bonig, H.; Münch, J. Absence of the CXCR4 Antagonist EPI-X4 from Pharmaceutical Human Serum Albumin Preparations. Preprints 2021, 2021030309 (doi: 10.20944/preprints202103.0309.v1). Gilg, A.; Harms, M.; Olari, L.; Urbanowitz, A.; Bonig, H.; Münch, J. Absence of the CXCR4 Antagonist EPI-X4 from Pharmaceutical Human Serum Albumin Preparations. Preprints 2021, 2021030309 (doi: 10.20944/preprints202103.0309.v1).

Abstract

Background: Endogenous Peptide Inhibitor of CXCR4 (EPI-X4) is a natural antagonist of the CXC chemokine receptor 4 (CXCR4). EPI-X4 is a 16-mer peptide that is released from human serum albumin (HSA) by acidic aspartic proteases such as Cathepsin D and E. Since human serum albumin (HSA) is an important medicinal substance we asked whether different pharmaceutical HSA products contain EPI-X4 which could have been generated during manufacturing and whether HSA can serve as a substrate for cathepsins despite of the presence of stabilizers like caprylate. Methods: Eight pharmaceutical HSA preparations representing all currently used fractionation technologies were analyzed. The previously described specific EPI-X4 ELISA was used for quantification; in vitro EPI-X4 generation by acidification in the presence or absence of cathepsins was followed by quantification with ELISA. Results: None of the pharmaceutical HSA preparations tested contained EPI-X4. Acidification of HSA did not generate EPI-X4. Addition of cathepsins D and E to acidified HSA yielded high concentrations of EPI-X4 in all HSA preparations, indistinguishable between individual products. Conclusion: Medicinal HSA preparations per se do not contain EPI-X4, but will replenish its precursor which can be cleaved to EPI-X4 in vivo, environmental conditions permitting.

Subject Areas

CXCR4; EPI-X4; human serum albumin

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