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

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:25

Article

Nakagawa, Yu^1,2  Watanabe, Yasunori¹  Igarashi, Yasuhiro³  Ito, Yukishige^2,4  Ojika, Makoto¹ 

[1] Nagoya Univ, Grad Sch Bioagr Sci, Dept Appl Mol Biosci, Chikusa Ku, Nagoya, Aichi 4648601, Japan

[2] RIKEN, Synthet Cellular Chem Lab, Wako, Saitama 3510198, Japan

[3] Toyama Prefectural Univ, Biotechnol Res Ctr, Imizu, Toyama 9390398, Japan

[4] Japan Sci & Technol Agcy, ERATO, Ito Glycotril Project, Wako, Saitama 3510198, Japan

关键词: Antibiotic;    Carbohydrate recognition;    Lectin;    Natural product;    Pradimicin;   

DOI  :  10.1016/j.bmcl.2015.05.021

来源: Elsevier

【 摘 要 】

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 H-1 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. (C) 2015 Elsevier Ltd. All rights reserved.

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