Heparin antiproliferative activity on bovine pulmonary artery smooth muscle cells requires both N-acetylation and N-sulfonation.
The antiproliferative activity of Heparin (HP) on bovine pulmonary artery smooth muscle cells (BPASMC) in vitro requires both N-acetylation and N-sulfonation. This was demonstrated by quantifying the relative N-acetylation of three commercial heparins of known antiproliferative activities, using their Fourier-transform infrared (FTIR) band areas at 1381-1378 and 1320-1317 cm(-1), which combined resulted in 1.0, 1.0 and 1.3 cm2 for Choay, Elkins-Sinn and Upjohn HP, respectively. These results show that Upjohn HP, which is at least 44% more antiproliferative than the other two, is 30% more N-acetylated. Upjohn HP was also N-desulfonated chemically, and its antiproliferative activity was determined. Its total sulfonate (--SO 3 -) content (O- and N-sulfonate) was quantified using the FTIR band area at 1260-1200 cm(-1) for the S=O stretching; a drop in sulfonate content from 21.87% (w/w) before N-desulfonation to 16.51% (w/w) after N-desulfonation, resulted in a 67% decrease in its inhibitory potency. In addition to the requirement that approximately 24% of the sulfonate content be bonded to N, the data show a direct correlation between the extent of Upjohn HP N-acetylation and its antiproliferative activity on BPASMC.
Longas
María O
MO
Purdue University Calumet, Department of Chemistry and Physics, Hammond, IN 46323, USA. mol@calumet.purdue.edu
Garg
Hari G
HG
Trinkle-Pereira
Jennifer M
JM
Hales
Charles A
CA
D000085:Acetates / Q000032:analysis; D000107:Acetylation; D000818:Animals; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D006493:Heparin / Q000737:chemistry* / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects; D011651:Pulmonary Artery / Q000166:cytology; D017550:Spectroscopy, Fourier Transform Infrared; D013329:Structure-Activity Relationship; D013451:Sulfonic Acids / Q000032:analysis
D000085:Acetates; D013451:Sulfonic Acids; D006493:Heparin