The growth promoter spermine interacts specifically with dermatan sulfate regions that are rich in L-iduronic acid and possess antiproliferative activity.
We have investigated interactions between spermine, a member of the growth promoting polyamine family, and various glycosaminoglycans. By using gel chromatography and equilibrium dialysis experiments we found that spermine binds to L-iduronic acid-rich dermatan sulfate (Kd, approximately 3.9 x 10(-4) M) with an affinity similar to that between spermine and DNA. By digesting spermine-dermatan sulfate complexes with chondroitin ABC lyase, the formation of oligosaccharide fragments (tetra-to-decasaccharides) was demonstrated by polyacrylamide gel electrophoresis. Chondroitin sulfate, which is deficient in L-iduronic acid, generates no spermine-protected fragments. Analysis of protected dermatan sulfate oligosaccharides indicates that the majority of the L-iduronic acid residue is non-sulfated and in a periodate-resistant conformation. The oligosaccharides also possess antiproliferative activity.
Belting
M
M
Department of Medical and Physiological Chemistry, University of Lund, Sweden.
Fransson
L A
LA
D002455:Cell Division / Q000187:drug effects; D002850:Chromatography, Gel; D003871:Dermatan Sulfate / Q000737:chemistry / Q000494:pharmacology*; D003956:Dialysis; D004347:Drug Interactions; D006131:Growth Inhibitors / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology*; D007067:Iduronic Acid / Q000032:analysis*; D013096:Spermine / Q000494:pharmacology*
D006131:Growth Inhibitors; D006133:Growth Substances; D003871:Dermatan Sulfate; D013096:Spermine; D007067:Iduronic Acid