Synthesis and pharmacological properties of a close analogue of an antithrombotic pentasaccharide (SR 90107A/ORG 31540).

The synthetic pentasaccharide (1) corresponding to the heparin sequence which binds to, and activates, antithrombin III (AT III) is a potent antithrombotic compound in several animal models of venous thrombosis. We describe here the preparation and the pharmacological properties of 34, an analogue of oligosaccharide 1 with the latter's N-sulfates being replaced by sulfate esters and hydroxyl groups being methylated. These structural modifications allow a simpler and more efficient synthesis of such anionic oligosaccharides.

Pharmacokinetic study of three synthetic AT-binding pentasaccharides in various animal species-extrapolation to humans.

The 'synthetic pentasaccharide', SR 90107A/Org 31540 (SP) representing the minimal AT-binding sequence of heparin is a catalyst of factor Xa inhibition. Affinity of SP, Sanorg 32701 (32701) and SR 80027 (80027), two close analogues of SP for rat, rabbit, baboon and human AT has been evaluated. The dissociation constants (Kd) for AT of the three species were in the range of 41-132, 1.

A unique trisaccharide sequence in heparin mediates the early step of antithrombin III activation.

Spectrofluorimetry experiments using synthetic trisaccharides indicate that in compounds that display affinity for antithrombin III (AT-III), a unique trisaccharide sequence plays the key role in the early recognition, and the first step of AT-III activation. Added to previous observations, these new results suggest that the two-step binding mechanism previously proposed (Olson et al., J.

Determination of the anti-factor Xa activity of the synthetic pentasaccharide SR 90107A/ORG 31540 and of two structural analogues.

The anti-factor Xa activity of the synthetic pentasaccharide SR 90107A/ORG 31540 was assayed by a chromogenic method at pH 8.4 and pH 7.35, comparatively to the 4th International Heparin Standard (IHS) or to the Ist International Low Molecular Weight Heparin Standard (LMWHS).

Entry and distribution of fluorescent antiproliferative heparin derivatives into rat vascular smooth muscle cells: comparison between heparin-sensitive and heparin-resistant cultures.

We studied the binding and entry of fluorescein (FITC)-labeled heparin derivatives into rat aortic smooth muscle cells (SMC) by confocal microscopy. FITC-labeled heparin fractions or FITC-labeled SR 80037A, a potent antiproliferative heparin derivative (Bârzu et al., Eur.