Restricted accessResearch articleFirst published online 1994-12
Design of a semi-synthetic (polymyxin-B•NHS-LC-biotin)4lavidin tetramer and evaluation of its ability to inhibit lipopolysaccharide induced TNFα synthesis
A method is described for the semi-synthetic production of (polymyxin-B•NHS-LC-biotin) 4lavidin tetramer. In phase I of semi-synthesis procedures, polymyxin-B was reacted with NHS-LC-biotin reagent resulting in the generation of the reactive intermediate, polymyxin-B•NHS-LC-biotin.
In phase II of the conjugation procedure, the polymyxin-B•NHS-LC-biotin complex was combined with purified avidin producing the tetramer complex, (polymyxin-B•NHS-LC-biotin) 4lavidin. A 'long-chain' biotinylation reagent, NHS-LC-biotin minimized steric hinderance phenomenon thereby maximizing the binding of multiple lipopolysaccharide molecules.
Binding avidity of (polymyxin-B•NHS-LC-biotin) 4lavidin for lipopolysaccharide was established with the application of fluorescein isothiocyanate Escherichia coli (055:B5) lipopolysaccharide conjugate (FITC-LPS). Applying a tissue culture based biological assay, (polymyxin-B•NHS-LC-biotin) 4lavidin was capable of inhibiting Salmonella minnesota (RS) lipopolysaccharide induced synthesis of tumor necrosis factorα (TNFα).
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