Determination of binding characteristics as a measure for effective albumin using different methods.

Autor: Paar M; Medical University of Graz, Otto Loewi Research Center, Division of Medicinal Chemistry, Neue Stiftingtalstrasse 6, 8010 Graz, Austria., Fengler VH; University of Graz, Institute of Molecular Biosciences, Humboldtstrasse 50, 8010 Graz, Austria., Reibnegger G; Medical University of Graz, Otto Loewi Research Center, Division of Medicinal Chemistry, Neue Stiftingtalstrasse 6, 8010 Graz, Austria., Schnurr K; MedInnovation GmbH, Wissenschaftsstandort Berlin-Adlershof (WISTA), Groß-Berliner Damm 151, 12487 Berlin, Germany., Waterstradt K; MedInnovation GmbH, Wissenschaftsstandort Berlin-Adlershof (WISTA), Groß-Berliner Damm 151, 12487 Berlin, Germany., Schwaminger SP; Medical University of Graz, Otto Loewi Research Center, Division of Medicinal Chemistry, Neue Stiftingtalstrasse 6, 8010 Graz, Austria; BioTechMed-Graz, Mozartgasse 12, 8010 Graz, Austria., Stauber RE; Medical University of Graz, Department of Internal Medicine, Division of Gastroenterology and Hepatology, Auenbruggerplatz 15, 8036 Graz, Austria., Oettl K; Medical University of Graz, Otto Loewi Research Center, Division of Medicinal Chemistry, Neue Stiftingtalstrasse 6, 8010 Graz, Austria. Electronic address: karl.oettl@medunigraz.at.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. General subjects [Biochim Biophys Acta Gen Subj] 2023 Sep; Vol. 1867 (9), pp. 130427. Date of Electronic Publication: 2023 Jul 15.
DOI: 10.1016/j.bbagen.2023.130427
Abstrakt: Background & Aims: Transport functions of albumin are of clinical and pharmacological interest and are determined by albumin's properties like posttranslational modifications or bound ligands. Both are affected in pathological conditions and in therapeutic grade albumin solutions. The term effective albumin concentration was introduced as a measure of functionally intact albumin. Our aim was to evaluate the impact of ligands and modifications with different approaches as a measure of effective albumin.
Approach & Results: We used a spin labelled fatty acid and dansylsarcosine to characterize binding properties of albumin i) prepared from plasma of patients and healthy control donors, ii) measured directly out of plasma, iii) research grade albumin, iv) in vitro modified albumin, and v) therapeutic infusion solutions before and after removal of stabilizers. Bilirubin is the main determinant for binding function in patients' albumin. In in vitro prepared albumin bound fatty acids correlated with impaired binding. Human nonmercaptalbumin1, not human nonmercaptalbumin2, showed reduced binding properties. Binding and transport function of therapeutic albumin was severely impaired and restored by filtration. Glycation of research grade albumin had no effect on the binding of dansylsarcosine and only a minor effect on fatty acid binding.
Conclusions: Our results suggest that effective albumin -in terms of binding properties- is primarily determined by bound ligands and only to a minor extent by posttranslational modifications. Characterizing albumin directly from plasma better reflects the physiological situation whereas in the case of therapeutic grade albumin stabilizers should be removed to make its binding properties accessible.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Karl Oettl is a consultant of Takeda Pharmaceuticals International AG.
(Copyright © 2023. Published by Elsevier B.V.)
Databáze: MEDLINE
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