Synthesis and biological activities of a library of glycosaminoglycans mimetic oligosaccharides.
Biologically active oligosaccharides related to glycosaminoglycans are accumulating increased attention because of their therapeutic potential and for their value in mechanistic studies. Heparan mimetics (HMs) are a family of dextran based polymer known to mimic the properties of glycosaminoglycans, and particularly those of heparan sulfates, as to interact with heparin binding proteins. HMs have shown to stimulate tissue repair in various animal models. Here, we use different methods to depolymerize HMs in order to produce a library of related oligosaccharides and study their biological activities. Since HMs were resistant to endoglycanases activities, depolymerization was achieved by chemical approaches. In vitro biological studies showed that HM oligosaccharides can differentially potentiate FGF-2 mitogenic and antithrombotic activities. In vivo, a selected oligosaccharide (H-dp12) showed to be able to regenerate tissue almost as well as the related polymeric product. The very low anticoagulant activity and high biological activity of low mass oligosaccharides give to these products a new therapeutic potential.
Laboratoire CRRET EAC CNRS 7149, Université Paris Est Créteil, Créteil, France.
Yasunori
Y
Ikeda
Saïd
S
Charef
Mohand-Ouidir
MO
Ouidja
Véronique
V
Barbier-Chassefière
Fernando
F
Sineriz
Arlette
A
Duchesnay
Hemalata
H
Narasimprakash
Isabelle
I
Martelly
Patrick
P
Kern
Denis
D
Barritault
Emmanuel
E
Petit
Dulce
D
Papy-Garcia
D000818:Animals; D002460:Cell Line; D006025:Glycosaminoglycans / Q000737:chemistry*; D006497:Heparan Sulfate / Q000737:chemistry; D008297:Male; D051379:Mice; D009844:Oligosaccharides / Q000737:chemistry* / Q000378:metabolism*; D012883:Skin Ulcer / Q000628:therapy; D023822:Tissue Engineering / Q000379:methods; D014945:Wound Healing / Q000502:physiology
D006025:Glycosaminoglycans; D006497:Heparan Sulfate; D009844:Oligosaccharides