Maurice Petitou

Chemical synthesis of heparin fragments and analogues.

The history of heparin dates back to 1916 when Jay Maclean, a PhD student in Howell’s laboratory, isolated an anticoagulant substance instead of the expected procoagulant phospholipids (1, 2). Since this substance was extracted from liver it was named heparin, in 1918, by Howell and Holt. Several years of debate then followed about the chemical nature of heparin (3). While it was initially thought to be a phospholipid, the polysaccharidic nature of heparin was suspected in 1925 and confirmed in the following years. However, the high complexity of the compound and the paucity of the analytical tools then available resulted in a very intricate situation where several authors proposed conflicting hypotheses regarding the nature of the different monosaccharides present as well as their substituents. It was only in the late 1960’s that the currently accepted chemical structure of heparin could be established (for a review, see (4)).

Biologically active heparin-like fragments with a “non-glycosamino”glycan structure. Part 1: a pentasaccharide containing a 3-O-methyl iduronic acid unit.

Abstract We describe a new approach towards biologically active analogues of glycosaminoglycan fragments where N-sulphates are replaced by O-sulphates and free hydroxyls are substituted by alkyl ethers. Here we demonstrate that introduction of a methyl group at the 3 position of L-iduronic acid residue neither affects the AT III mediated anti-factor Xa activity nor alters the conformational properties of a unique haparin pentasaccharide sequence.

Biological properties of synthetic glycoconjugate mimics of heparin comprising different molecular spacers

The in vitro antithrombotic activity of synthetic glycoconjugates I and II, comprising a flexible polyethylene glycol type and a rigid polyglucose type spacer, respectively, are compared to heparin.

Heparin: from the original "soup" to well-designed heparin mimetics

Since its introduction in 1937 heparinotherapy has improved consistently. In this article we describe the rationale behind the different steps of the evolution that, starting from a very impure polysaccharide mixture, ended in the proposal for development of pure synthetic antithrombotic oligosaccharides.

Synthesis of a dermatan sulphate-like hexasaccharide with a “non-glycosamino” glycan structure

Abstract The synthesis of a “non-glycosamino” glycan counterpart (i.e. compound II ) of a naturally occuring dermatan sulphate hexasaccharide that binds with high affinity to heparin cofactor II is described.

A synthetic heparin/heparan sulfate-like decasaccharide releases lipase activity in vivo. Chemical synthesis and biological activity

Abstract A decasaccharide mimic of the heparan sulfate fragment reported to have high affinity for lipoprotein lipase has been synthesised, and shown to release lipase activity in vivo in the rat.