Increased inter dimeric interaction of oxy hemoglobin is necessary for attenuation of reductive pegylation promoted dissociation of tetramer.
The propensity of site-specific carboxymethylation and propylation of Val-1(α) of Hb to attenuate the reductive hexaPEGylation-induced dissociation of tetramers has been investigated. Only reductive propylation of Val-1(α), which increases the stability of oxy Hb, attenuates the reductive hexaPEGylation-induced dissociation. Increasing the stability of the oxy conformation of Hb by chemical or genetic approaches is a strategy to generate PEGylated Hbs with native-like tetramer stability using direct PEGylation platforms. This new approach and EAF-PEGylation are the only two alternate PEGylation strategies available to design stable second-generation vasoinactive uncrosslinked PEGylated Hbs with native-like tetramer stability.
Hu
Tao
T
Department of Physiology and Biophysics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Li
Dongxia
D
Meng
Fantao
F
Prabhakaran
Muthuchidambaram
M
Acharya
Seetharama A
SA
D000447:Aldehydes / Q000737:chemistry*; D000494:Allosteric Regulation; D002850:Chromatography, Gel / Q000379:methods; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006038:Glyoxylates / Q000737:chemistry*; D010100:Oxygen / Q000737:chemistry* / Q000378:metabolism; D010108:Oxyhemoglobins / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D055550:Protein Stability; D020836:Protein Structure, Quaternary; D014633:Valine / Q000737:chemistry* / Q000378:metabolism
D000447:Aldehydes; D006038:Glyoxylates; D010108:Oxyhemoglobins; D011108:Polymers; D011092:Polyethylene Glycols; C005556:propionaldehyde; D014633:Valine; C031150:glyoxylic acid; D010100:Oxygen