A covalently linked recombinant albumin dimer is more rapidly cleared in vivo than are wild-type and mutant C34A albumin

McCurdy, Teresa R.; Gataiance, Sharon; Eltringham-Smith, Louise J.; Sheffield, William P.

doi:10.1016/j.lab.2003.10.008

Cited by 18 publications

(14 citation statements)

References 33 publications

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“…In contrast to our observations, McCurdy et al (32) showed that a recombinant rabbit albumin (RSA) dimer consisting of N-terminal hexahistidinyl tagRSA(C34A) joined to G6 joined to RSA containing the C34A mutation in that order, from the N-terminus to the C-terminus, is more rapidly cleared in vivo than wild-type and mutant C34A rabbit albumins. The authors concluded from their study that albumin dimerization does not look promising as a tool to slow clearance.…”

Section: Discussioncontrasting

confidence: 99%

Recombinant Human Serum Albumin Dimer has High Blood Circulation Activity and Low Vascular Permeability in Comparison with Native Human Serum Albumin

et al. 2006

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Purpose. Human serum albumin (HSA) is used clinically as an important plasma expander. Albumin infusion is not recommended for critically ill patients with hypovolemia, burns, or hypoalbuminemia because of the increased leakage of albumin into the extravascular spaces, thereby worsening edema. In the present study, we attempted to overcome this problem by producing a recombinant HSA (rHSA) dimer with decreased vascular permeability and an increased half-life. Methods. Two molecules of rHSA were genetically fused to produce a recombinant albumin dimer molecule. The pharmacokinetics and biodistribution of the recombinant proteins were evaluated in normal rats and carrageenin-induced paw edema mouse model. Results. The conformational properties of this rHSA dimer were similar to those for the native HSA (the HSA monomer), as evidenced by the Western blot and spectroscopic studies. The biological halflife and area under the plasma concentrationYtime curve of the rHSA dimer were approximately 1.5 times greater than those of the monomer. Dimerization has also caused a significant decrease in the total body clearance and distribution volume at the steady state of the native HSA. rHSA dimer accumulated to a lesser extent in the liver, skin, muscle, and fat, as compared with the native HSA. Up to 96 h, the vascular permeability of the rHSA dimer was less than that of the native HSA in paw edema mouse models. A prolonged plasma half-life of the rHSA dimer was also observed in the edema model rats. Conclusions. rHSA dimer has a high retention rate in circulating blood and a lower vascular permeability than that of the native HSA.

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Section: Discussioncontrasting

confidence: 99%

Recombinant Human Serum Albumin Dimer has High Blood Circulation Activity and Low Vascular Permeability in Comparison with Native Human Serum Albumin

et al. 2006

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“…For instance, the half-life of GP62 polypeptide increased twofold when the reaction mixture contained 600 mm HSA, which was equivalent to the concentration in the human bloodstream. [15] Similar results were also obtained for FXa-mediated hydrolysis of polypeptides containing FXa-cleavable linker, that is, IE3, IE6, and IE8 (Figure 2 a). Furthermore, the half-lives for the polypeptides containing TBN-cleavable linkers were examined against both TBN and DPP4 (Supporting Information, Table S1).…”

supporting

confidence: 78%

“…[6,7] Of these strategies, coupling a bioactive peptide to a plasma protein, or a protein domain that can associate with a plasma protein, shows promise for extending the peptide half-life. [8][9][10][11][12][13][14] Human serum albumin (HSA) is an endogenous molecule transporter with a half-life of 19 days, [15] and thereby HSA has unique advantages over other plasma proteins as a drug carrier for improving the half-life of therapeutic peptides. [9] However, coupling to HSA often reduces peptide bioactivity in the fusion form.…”

mentioning

confidence: 99%

A Protease‐Based Strategy for the Controlled Release of Therapeutic Peptides

Li¹,

Ma²,

Chen³

et al. 2010

Angew Chem Int Ed

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“…The result showed that the biological half-life the rHSA dimer was approximately 1.5 times greater and the vascular permeability of the rHSA dimer was less than that of the native HSA in paw edema mouse models. 8) In contrast to their observations, a previous study showed that a covalently linked recombinant albumin dimer was more rapidly cleared in vivo than wild-type albumin, 32) they contributed this to the role for the reticuloendothelial system in the differential clearance of the larger protein. The present study evaluated the pharmacokinetics of PEG-HSA in a mouse system, the results showed that plasma half-life of modified HSA was 21.91±2.00 h, 2.3 times greater than the native protein.…”

Section: Discussionmentioning

confidence: 69%

Site-Specific Chemical Modification of Human Serum Albumin with Polyethylene Glycol Prolongs Half-life and Improves Intravascular Retention in Mice

Zhao

Cheng

Tan

et al. 2012

Biological & Pharmaceutical Bulletin

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Human serum albumin (HSA) is used as an important plasma volume expander in clinical practice. However, the infused HSA may extravasate into the interstitial space and induce peripheral edema in treating the critical illness related to marked increase in capillary permeability. Such poor intravascular retention also demands a frequent administration of HSA. We hypothesize that increasing the molecular weight of HSA by PEGylation may be a potential approach to decrease capillary permeability of HSA. In the present study, HSA was PEGylated in a site-specific manner and the PEGylated HSA carrying one chain of polyethylene glycol (PEG) (20 kDa) per HSA molecule was obtained. The purity, PEGylated site and secondary structure of the modified protein were characterized by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), thiol group blockage method and circular dichroism (CD) measurement, respectively. In addition, the pharmacokinetics in normal mice was investigated, vascular permeability of the PEGylated HSA was evaluated in lipopolysaccharide (LPS)-induced lung injury mouse model and the pharmacodynamics was investigated in LPS-induced sepsis model with systemic capillary leakage. The results showed that the biological half-life of the modified HSA was approximately 2.3 times of that of the native HSA, PEG-HSA had a lower vascular permeability and better recovery in blood pressure and haemodilution was observed in rats treated with PEG-HSA. From the results it can be inferred that the chemically well-defined and molecularly homogeneous PEGylated HSA is superior to HSA in treating capillary permeability increase related illness because of its longer biological half-life and lower vascular permeability.

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A covalently linked recombinant albumin dimer is more rapidly cleared in vivo than are wild-type and mutant C34A albumin

Cited by 18 publications

References 33 publications

Recombinant Human Serum Albumin Dimer has High Blood Circulation Activity and Low Vascular Permeability in Comparison with Native Human Serum Albumin

Recombinant Human Serum Albumin Dimer has High Blood Circulation Activity and Low Vascular Permeability in Comparison with Native Human Serum Albumin

A Protease‐Based Strategy for the Controlled Release of Therapeutic Peptides

Site-Specific Chemical Modification of Human Serum Albumin with Polyethylene Glycol Prolongs Half-life and Improves Intravascular Retention in Mice

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