Introduction of negative charges to a crosslinked hemoglobin: lack of effect on plasma half time.
Intramolecularly crosslinked hemoglobins do not dissociate into alpha 1 beta 1 dimers. As a result, they escape glomerular filtration and have plasma half times of 4 hours. This value is shorter than for albumin (5.2 hours) with similar molecular weight but higher negative charge. The present study was done to determine if increased negative charge on a hemoglobin covalently crosslinked with bis (3,5-dibromosalicyl) sebacate would lengthen its plasma half time. Negative charge was introduced by acylation with succinic anhydride. The product had a higher negative charge; however, plasma half time was not increased. A larger fraction of the succinylated material was excreted in the urine suggesting molecular instability.
Thomas
M
M
Department of Physiology (Dental School), University of Maryland at Baltimore 21201, USA.
Matheson-Urbaitis
B
B
Kwansa
H
H
Bucci
E
E
Fronticelli
C
C
D000818:Animals; D001794:Blood Pressure; D002850:Chromatography, Gel; D003432:Cross-Linking Reagents / Q000737:chemistry / Q000493:pharmacokinetics*; D003652:Decanoic Acids / Q000737:chemistry / Q000493:pharmacokinetics*; D004553:Electric Conductivity; D005078:Exchange Transfusion, Whole Blood; D006454:Hemoglobins / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012459:Salicylates / Q000737:chemistry / Q000493:pharmacokinetics*
D003432:Cross-Linking Reagents; D003652:Decanoic Acids; D006454:Hemoglobins; D012459:Salicylates; C089663:bis(3,5-dibromosalicyl)sebacate