Development and validation of a HPAE-PAD method for the quantification of CGP69669A, a sialyl Lewis(x) mimetic, in skin permeation studies

A simple, rapid, precise and specific isocratic HPAE‐PAD method for quantification of CGP69669A was developed and validated. CGP69669A is a glycomimetic of sialyl Lewis^x and an antagonist of E‐selectin with potential application in the treatment of inflammatory skin disease. Quantification was performed using a Dionex CarboPac^TM PA‐200 anion‐exchange column (3 × 250 mm) with 100 mm NaOH solution as mobile phase, a flow rate of 0.50 mL/min and an injection volume of 10 μL. A quadruple potential waveform was used to detect the carbohydrate (+0.1 V from 0.00 to 0.40 s, ?2.0 V from 0.41 to 0.42 s, +0.6 V at 0.43 s and ?0.1 V from 0.44 to 0.50 s with current integrated between 0.20 and 0.40 s for detection) and rafinose was employed as an internal standard. The optimized conditions enabled rapid elution of CGP69669A (at 3.0 min) without interference from solvent peaks or substances present in the skin. The method showed good intra‐ and inter‐day precision and accuracy and the response was linear from 1.0 to 25 µg/mL. This is the first validated direct method for the quantification of CGP69669A. It will now be employed in studies investigating the topical and transdermal delivery of CGP69669A in vitro and in vivo and it should also be of use for other applications of this molecule. Copyright © 2011 John Wiley & Sons, Ltd.     

The First Total Synthesis of 6-Sulfo-de-N-acetylsialyl Lewisx Ganglioside: A Superior Ligand for Human L-Selectin

Originally discovered as a minor by-product of 6-sulfo-N-acetylsialyl Lewis^x, the de-N-acetylated form 1 is a superior L-selectin ligand to the N-acetyl form. To substantiate the extraordinary reactivity of 1 , it was synthesized for the first time and its binding to L-selectin investigated. Compound 1 and related structures may be high-affinity endogenous ligands for L-selectin that are involved in the interaction of leukocytes with the vascular endothelium.