Chemical Modifications of Heparin.1: Reaction of Partially N-Desulfated Heparin with Glutaraldehyde

Abstract

Purified glutaraldehyde was allowed to react with the primary amino groups generated by mild acidolysis of glucosamine N -sulfamino residues present in heparinic acid. The reaction yielded high molecular mass heparinoids (HMMHEP) or hydrogels, depending on experimental conditions. It was shown that a selected HMMHEP exhibited a higher anticoagulant activity than the starting heparin or the parent partially N -desulfated heparin. This HMMHEP degraded slowly in vitro in an aqueous medium buffered at pH = 7.4. Moreover, HMMHEP was biologically active after i.v. injection but not after s.c. and i.m. injections. Hydrogels also degraded slowly to yield biologically active higher molecular mass heparinoid. These findings suggested that neither N -desulfation nor coupling of glutaraldehyde adducts affected in a large extend the activity of the parent heparin.

Chemical Derivatization of Sulfated Glycosaminoglycans

“…Partially de‐ N ‐sulfated heparins have been exploited to generate imines with dialdehydes such as glutaraldehyde or with long‐chain aldehydes such as dodecanal . The resulting conjugates were screened for their anticoagulant activity.…”

Molecular engineering of glycosaminoglycan chemistry for biomolecule delivery

“…However, some reports focus on the preparation of selectively N-desulfated heparin [119, 129] which could be used for mechanistic studies of protein interactions and molecular delivery, because N-desulfated heparin/HS loses a large portion of its anticoagulant activity (3–5 times less than regular heparin) [130]. Crosslinking of N-desulfated heparin with glutaraldehyde under formation of high molar mass polymers or hydrogels was reported as well [131]. …”

Poly(DL‐lactic acid) film surface modification with heparin for improving hemocompatibility of blood‐contacting bioresorbable devices

“…Indeed, it has been previously shown that heparin retained its anticoagulant activity even after drastic chemical modifications as long as these modifications did not involve N‐desulfatation. 20…”

“…Indeed, it has been previously shown that heparin retained its anticoagulant activity even after drastic chemical modifications as long as these modifications did not involve N-desulfatation. 20 Antifactor Xa activity. Heparin activity was assessed by measuring antifactor Xa activity according to USP 28 monography.…”