title: New insights into in vitro amyloidogenic properties of human serum albumin suggest considerations for therapeutic precautions.
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.
authors.affiliation: Department of Biotechnology, Indian Institute of Technology Hyderabad, ODF Estate, Yeddumailaram, Medak Dist, Telangana 502205, India.
authors.forename: Neetu
authors.initials: N
authors.lastname: Sharma
authors.affiliation: Department of Biotechnology, Indian Institute of Technology Hyderabad, ODF Estate, Yeddumailaram, Medak Dist, Telangana 502205, India.
authors.forename: Vishwanath
authors.initials: V
authors.lastname: Sivalingam
authors.affiliation: Department of Biotechnology, Indian Institute of Technology Hyderabad, ODF Estate, Yeddumailaram, Medak Dist, Telangana 502205, India.
authors.forename: Sonalika
authors.initials: S
authors.lastname: Maurya
authors.affiliation: Department of Biotechnology, Indian Institute of Technology Hyderabad, ODF Estate, Yeddumailaram, Medak Dist, Telangana 502205, India.
authors.forename: Archana
authors.initials: A
authors.lastname: Prasad
authors.affiliation: Physical and Materials Chemistry Division, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411008, India.
authors.forename: Puneet
authors.initials: P
authors.lastname: Khandelwal
authors.affiliation: Department of Anatomy, All India Institute of Medical Sciences, New Delhi 110029, India.
authors.forename: Subhash Chandra
authors.initials: SC
authors.lastname: Yadav
authors.affiliation: Department of Biotechnology, Indian Institute of Technology Hyderabad, ODF Estate, Yeddumailaram, Medak Dist, Telangana 502205, India. Electronic address: basantkpatel@iith.ac.in.
authors.forename: Basant K
authors.initials: BK
authors.lastname: Patel
mesh_terms: D058227:Amyloidogenic Proteins / Q000009:adverse effects / Q000737:chemistry* / Q000235:genetics / Q000648:ultrastructure; D002850:Chromatography, Gel; D003545:Cysteine / Q000737:chemistry; D003902:Detergents / Q000737:chemistry; D019281:Dimerization; D004337:Drug Carriers; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry; D018625:Microscopy, Atomic Force; D046529:Microscopy, Electron, Transmission; D008970:Molecular Weight; D016877:Oxidants / Q000737:chemistry; D010084:Oxidation-Reduction; D010952:Plasma Substitutes / Q000009:adverse effects / Q000737:chemistry*; D066263:Protein Aggregation, Pathological / Q000209:etiology; D055550:Protein Stability; D011994:Recombinant Proteins; D012521:Sarcosine / Q000031:analogs & derivatives / Q000737:chemistry; D012709:Serum Albumin / Q000009:adverse effects / Q000737:chemistry* / Q000235:genetics / Q000648:ultrastructure; D000075462:Serum Albumin, Human
chemical_list: C422455:ALB protein, human; D058227:Amyloidogenic Proteins; D003902:Detergents; D004337:Drug Carriers; D016877:Oxidants; D010952:Plasma Substitutes; D011994:Recombinant Proteins; D012709:Serum Albumin; C025231:sarkosyl; D006861:Hydrogen Peroxide; D003545:Cysteine; D012521:Sarcosine; D000075462:Serum Albumin, Human
keywords: Drug carrier; HSA amyloid; Plasma expander; Sarkosyl; Self-seeding