Evidence map›Paper›PMID 31748894›Full record

ArticlePharmaceutical research2019

Stability and Biological Activity of E. coli Derived Soluble and Precipitated Bone Morphogenetic Protein-2.

Bastian Quaas, Laura Burmeister, Zhaopeng Li, Alexandra Satalov, Peter Behrens, Andrea Hoffmann, Ursula Rinas

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Article in Pharmaceutical research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.9field-weighted citation impact, top 27% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 14 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 4 institutions in 2 countries.

Bastian QuaasLeibniz University of Hannover, Technical Chemistry - Life Science, Hannover, Germany.
Laura BurmeisterHannover Medical School, Department of Orthopedic Surgery Graded Implants and Regenerative Strategies, Laboratory of Biomechanics and Biomaterials, Hannover, Germany.
Zhaopeng LiLeibniz University of Hannover, Technical Chemistry - Life Science, Hannover, Germany.
Alexandra SatalovLeibniz University Hannover, Institute for Inorganic Chemistry, Hannover, Germany.
Peter BehrensLower Saxony Center for Biomedical Engineering Implant Research and Development, Hannover, Germany.
Andrea HoffmannHannover Medical School, Department of Orthopedic Surgery Graded Implants and Regenerative Strategies, Laboratory of Biomechanics and Biomaterials, Hannover, Germany.
Ursula RinasLeibniz University of Hannover, Technical Chemistry - Life Science, Hannover, Germany. Ursula.Rinas@helmholtz-hzi.de.
Leibniz University Hannover · DEMedizinische Hochschule Hannover · DEHelmholtz Centre for Infection Research · DEPasargad Institute for Advanced Innovative Solutions · IR

Funding

Deutsche Forschungsgemeinschaft Exzellenzcluster "Rebirth" EXC62Deutsche Forschungsgemeinschaft FOR2180
6 · The paper itself

Abstract

purposeThere is a plethora of studies on recombinant human bone morphogenetic protein-2 (rhBMP-2) application and delivery systems, but surprisingly few reports address the biophysical properties of the protein which are of crucial importance to develop effective delivery systems or to solve general problems related to rhBMP-2 production, purification, analysis and application.

methodsThe solubility, stability and bioactivity of rhBMP-2 obtained by renaturation of E. coli derived inclusion bodies was assessed at different pH and in different buffer systems using (dynamic) light scattering and thermal shift assays as well as intrinsic fluorescence measurements and luciferase based bioassays.

resultsrhBMP-2 is poorly soluble at physiological pH and higher. The presence of divalent anions further decreases the solubility even under acidic conditions. Thermal stability analyses revealed that rhBMP-2 precipitates are more stable compared to the soluble protein. Moreover, correctly folded rhBMP-2 is also bioactive as precipitated protein and precipitates readily dissolve under appropriate buffer conditions. Once properly formed rhBMP-2 also retains biological activity after temporary exposure to high concentrations of chaotropic denaturants. However, care should be taken to discriminate bioactive rhBMP-2 precipitates from misfolded rhBMP-2 aggregates, e.g. resolvability in MES buffer (pH 5) and a discrete peak in thermoshift experiments are mandatory for correctly folded rhBMP-2.

conclusionsOur analysis revealed that E. coli derived rhBMP-2 precipitates are not only bioactive but are also more stable compared to the soluble dimeric molecules. Knowledge about these unusual properties will be helpful to design improved delivery systems requiring lower amounts of rhBMP-2 in clinical applications.

Indexed as

Bone Morphogenetic Protein 2Escherichia coliHeparinHumansHydrogen-Ion ConcentrationOsmolar ConcentrationOxalatesParticle SizeProtein AggregatesProtein ConformationProtein FoldingProtein StabilityRecombinant ProteinsSodium ChlorideSolubilityTemperatureBone Morphogenetic Protein 2HeparinOxalatesProtein Aggregatesrecombinant human bone morphogenetic protein-2Recombinant ProteinsSodium ChlorideTransforming Growth Factor betaprotein aggregationprotein solubilityprotein stabilityrecombinant human bone morphogenetic protein-2refolding

Identifiers

PMID31748894
OpenAlexW2991509617

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.