INHIBITION OF THE ALPHA-L-ARABINOFURANOSIDASE-III OF MONILINIA-FRUCTIGENA BY 1,4-DIDEOXY-1,4-IMINO-L-THREITOL AND 1,4-DIDEOXY-1,4-IMINO-L-ARABINITOL
INHIBITION OF THE ALPHA-L-ARABINOFURANOSIDASE-III OF MONILINIA-FRUCTIGENA BY 1,4-DIDEOXY-1,4-IMINO-L-THREITOL AND 1,4-DIDEOXY-1,4-IMINO-L-ARABINITOL
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DOI：
10.1042/bj2660245
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发表时间：
1990-02-15
影响因子：
4.1
通讯作者：
SINNOTT, ML
中科院分区：
文献类型：
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作者：
AXAMAWATY, MTH;FLEET, GWJ;SINNOTT, ML
1.合成了1，4-二脱氧-1，4-亚氨基-L-苏糖醇，改进了1，4-二脱氧-1，4-亚氨基-L-阿拉伯糖醇的合成工艺。2.这两种化合物都是褐腐病菌α- L-阿拉伯呋喃糖苷酶III，阿拉伯糖醇中的额外羟甲基对结合吉布斯自由能贡献约17.8 kJ/mol（4.25 kcal/mol）。3.这两种化合物的亲和力（1/Ki）均随pH值呈经典的钟形变化，PKa值为酶上的酸催化基团[5，9; Selwood和Sinnott（1988）Biochem. J. 254，899-901]，pKb值为游离抑制剂的值，分别为7.6和7.8。4.在这些和文献数据的基础上，我们建议，有效地抑制糖苷酶在其pH值的适当iminoalditol将被发现时，iminoalditol的pKa是低于目标酶的酸催化基团。
1. 1,4-Dideoxy-1,4-imino-L-threitol was synthesized and the synthesis of 1,4-dideoxy-1,4-imino-L-arabinitol was improved. 2. Both compounds are competitive inhibitors of Monilinia fructigena .alpha.-L-arabino-furanosidase III, the additional hydroxymethyl group in the arabinitol contributing about 17.8 kJ/mol (4.25 kcal/mol) to the Gibbs free energy of binding. 3. The affinities (1/Ki) of both compounds vary with pH in a classical bell-shaped way, the pKa value being that the acid-catalytic group on the enzyme [5,9; Selwood and Sinnott (1988) Biochem. J. 254, 899-901] and the pKb values being those of the free inhibitors, 7.6 and 7.8 respectively. 4. On the basis of these and literature data we suggest that efficient inhibition of glycosidase at its pH by an appropriate iminoalditol will be found when the pKa of the iminoalditol is below that of the acid-catalytic group of the target enzyme.