Glycosaminoglycan mimetic biomaterials. 4. Synthesis of sulfated lactose-based glycopolymers that exhibit anticoagulant activity.
Cyanoxyl persistent radicals can be used as chain-growth moderators of the statistical copolymerization of a variety of monomers. We report herein the preparation of fully sulfated lactose-based glycopolymers by cyanoxyl (.OC[triple bond]N)-mediated free-radical polymerization of acrylamide derivatized glycomonomers in good yield (60-80%) and low polydispersity (1.1 < M(w)/M(n) < 1.6). Prolongation of the activated partial thromboplastin time (aPTT) was observed, and structure-activity relationships were defined. Specifically, the anticoagulant effect varied in response to both polymer molecular weight and the density of pendant sulfated lactose units. Nonetheless, measured thrombin times were only modestly prolonged suggesting that the observed anticoagulant effect is not primarily related to direct thrombin inhibition.
Sun
Xue-Long
XL
Laboratory for Biomolecular Materials Research, Departments of Surgery and Bioengineering, Emory University School of Medicine, 1639 Pierce Drive, Atlanta, GA 30322, USA.
Grande
Daniel
D
Baskaran
Subramanian
S
Hanson
Stephen R
SR
Chaikof
Elliot L
EL
D000180:Acrylic Resins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000925:Anticoagulants / Q000138:chemical synthesis* / Q000494:pharmacology; D001672:Biocompatible Materials / Q000138:chemical synthesis*; D001777:Blood Coagulation / Q000187:drug effects; D006025:Glycosaminoglycans / Q000138:chemical synthesis*; D006801:Humans; D007785:Lactose / Q000737:chemistry; D010314:Partial Thromboplastin Time; D013329:Structure-Activity Relationship; D013431:Sulfates / Q000737:chemistry; D000099166:Polyacrylamides
D000180:Acrylic Resins; D000925:Anticoagulants; D001672:Biocompatible Materials; D006025:Glycosaminoglycans; D007785:Lactose; D013431:Sulfates; D000099166:Polyacrylamides