Premium
New insights into in vitro amyloidogenic properties of human serum albumin suggest considerations for therapeutic precautions
Author(s) -
Sharma Neetu,
Sivalingam Vishwanath,
Maurya Sonalika,
Prasad Archana,
Khandelwal Puneet,
Yadav Subhash Chandra,
Patel Basant K.
Publication year - 2015
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2015.11.004
Subject(s) - human serum albumin , chemistry , amyloid (mycology) , monomer , in vitro , biophysics , seeding , albumin , cysteine , drug , biochemistry , chromatography , pharmacology , medicine , biology , organic chemistry , polymer , inorganic chemistry , agronomy , enzyme
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.