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PMID:26554815

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Citation

Sharma, N, Sivalingam, V, Maurya, S, Prasad, A, Khandelwal, P, Yadav, SC and Patel, BK (2015) New insights into in vitro amyloidogenic properties of human serum albumin suggest considerations for therapeutic precautions. FEBS Lett. 589:4033-8

Abstract

Amyloid aggregates display striking features of detergent stability and self-seeding. Human serum albumin (HSA), a preferred drug-carrier molecule, can also aggregate in vitro. So far, key amyloid properties of stability against ionic detergents and self-seeding, are unclear for HSA aggregates. Precautions against amyloid contamination would be required if HSA aggregates were self-seeding. Here, we show that HSA aggregates display detergent sarkosyl stability and have self-seeding potential. HSA dimer is preferable for clinical applications due to its longer retention in circulation and lesser oedema owing to its larger molecular size. Here, HSA was homodimerized via free cysteine-34, without any potentially immunogenic cross-linkers that are usually pre-requisite for homodimerization. Alike the monomer, HSA dimers also aggregated as amyloid, necessitating precautions while using for therapeutics.

Links

PubMed Online version:10.1016/j.febslet.2015.11.004

Keywords

Amyloidogenic Proteins/adverse effects; Amyloidogenic Proteins/chemistry; Amyloidogenic Proteins/genetics; Amyloidogenic Proteins/ultrastructure; Chromatography, Gel; Cysteine/chemistry; Detergents/chemistry; Dimerization; Drug Carriers; Humans; Hydrogen Peroxide/chemistry; Microscopy, Atomic Force; Microscopy, Electron, Transmission; Molecular Weight; Oxidants/chemistry; Oxidation-Reduction; Plasma Substitutes/adverse effects; Plasma Substitutes/chemistry; Protein Aggregation, Pathological/etiology; Protein Stability; Recombinant Proteins; Sarcosine/analogs & derivatives; Sarcosine/chemistry; Serum Albumin/adverse effects; Serum Albumin/chemistry; Serum Albumin/genetics; Serum Albumin/ultrastructure; Serum Albumin, Human

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:ALBU

enables

GO:0042802: identical protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P02768

F

Seeded From UniProt

complete

Notes

See also

References

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