Pradimicin A, a d-mannose-binding antibiotic, binds pyranosides of l-fucose and l-galactose in a calcium-sensitive manner

Pradimicin A (PRM-A) is a unique antibiotic with a lectin-like ability to bind d-mannose (d-Man) in the presence of Ca2+ ion. Although accumulated evidences suggest that PRM-A recognizes the 2-, 3-, and 4-hydroxyl groups of d-Man, BMY-28864, an artificial PRM-A derivative, was shown not to bind l-fucose (l-Fuc) and l-galactose (l-Gal), both of which share the characteristic array of the three hydroxyl groups with d-Man. To obtain a plausible explanation for this inconsistency, we performed co-precipitation experiments of PRM-A with l-Fuc, l-Gal, and their methyl pyranosides (l-Fuc-OMe, l-Gal-OMe) by taking advantage of aggregate-forming propensity of the binary [PRM-A/Ca2+] complex. While l-Fuc and l-Gal were hardly incorporated into the aggregate, l-Fuc-OMe and l-Gal-OMe were found to exhibit significant binding to PRM-A. However, increased Ca2+ concentration abolished this binding, raising the possibility that poor binding of l-Fuc and l-Gal to PRM-A is attributed to their chelation with Ca2+ ion. This possibility was partly supported by 1H NMR analysis that detected interaction of l-Fuc and l-Gal with Ca2+ ion in aqueous solution. These results collectively indicate that PRM-A binds pyranosides of l-Fuc and l-Gal when Ca2+ concentration is not excessive to trap these sugars by chelation but sufficient to form the [PRM-A/Ca2+] complex.

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