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C(1)-/C(2)-aromatic-imino-glyco-conjugates: experimental and computational studies of binding, inhibition and docking aspects towards glycosidases isolated from soybean and jack bean

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Title C(1)-/C(2)-aromatic-imino-glyco-conjugates: experimental and computational studies of binding, inhibition and docking aspects towards glycosidases isolated from soybean and jack bean
 
Creator KUMAR, A
SINGHAL, NK
RAMANUJAM, B
MITRA, A
RAMESHWARAM, NR
NADIMPALLI, SK
RAO, CP
 
Subject crystal-structure
5-membered iminocyclitol
alpha-galactosidase
beta-glucosidase
emerging class
potent
mannosidase
derivatives
complex
amino(hydroxymethyl)cyclopen-tanetriols
c1-/c2-aromatic-imino-glyco-conjugates
glycosidase inhibition
pure alpha-mannosidase
rigid docking
fluorescence quenching
glycosidases from soybean and jack bean
 
Description Several C(1)-imino conjugates of d-galactose, d-lactose and d-ribose, where the nitrogen center was substituted by the salicylidene or naphthylidene, were synthesized and characterized. Similar C(2)-imino conjugates of d-glucose have also been synthesized. All the glyco-imino-conjugates, which are transition state analogues, exhibited 100% inhibition of the activity towards glycosidases extracted from soybean and jack bean meal. Among these, a galactosyl-napthyl-imine-conjugate (1c) showed 50% inhibition of the activity of pure alpha-mannosidase from jack bean at 22 +/- 2.5 mu M, and a ribosyl-naphthyl-imine-conjugate (3c) showed at 31 +/- 5.5 mu M and hence these conjugates are potent inhibitors of glycosidases. The kinetic studies suggested non-competitive inhibition by these conjugates. The studies are also suggestive of the involvement of aromatic, imine and carbohydrate moieties of the glyco-imino-conjugates in the effective inhibition. The binding of glyco-imino-conjugate has been established by extensive studies carried out using fluorescence emission and isothermal titration calorimetry. The conformational changes resulted in the enzyme upon interaction of these derivatives has been established by studying the fluorescence quench of the enzyme by KI as well as from the secondary structural changes noticed in CD spectra. All these studies revealed the difference in the binding strengths of the naphthylidene vs. salicylidene as well as galactosyl vs. lactosyl moieties present in these conjugates. The differential inhibition of these glyco-conjugates has been addressed by quantifying the specific interactions present between the glyco-conjugates and the enzyme by using rigid docking studies.
 
Publisher SPRINGER
 
Date 2011-08-29T10:32:38Z
2011-12-26T12:58:33Z
2011-12-27T05:48:42Z
2011-08-29T10:32:38Z
2011-12-26T12:58:33Z
2011-12-27T05:48:42Z
2009
 
Type Article
 
Identifier GLYCOCONJUGATE JOURNAL, 26(4), 495-510
0282-0080
http://dx.doi.org/10.1007/s10719-008-9199-4
http://dspace.library.iitb.ac.in/xmlui/handle/10054/12054
http://hdl.handle.net/10054/12054
 
Language en