Abstract
We previously reported on the preparation of supramolecular complexes by the 2:2:2 assembly of a dinuclear Zn2+-cyclen (cyclen = 1,4,7,10-tetraazacyclododecane) complex having a 2,2′-bipyridyl linker equipped with 0~2 long alkyl chains (Zn2L1~Zn2L3), 5,5-diethylbarbituric acid (Bar) derivatives, and a copper(II) ion (Cu2+) in aqueous solution and two-phase solvent systems and their phosphatase activities for the hydrolysis of mono(4-nitrophenyl) phosphate (MNP). These supermolecules contain Cu2(μ-OH)2 core that mimics the active site of alkaline phosphatase (AP), and one of the ethyl groups of the barbital moiety is located in close proximity to the Cu2(μ-OH)2 core. The generally accepted knowledge that the amino acids around the metal center in the active site of AP play important roles in its hydrolytic activity inspired us to modify the side chain of Bar with various functional groups in an attempt to mimic the active site of AP in the artificial system, especially in two-phase solvent system. In this paper, we report on the design and synthesis of new supramolecular complexes that are prepared by the combined use of bis(Zn2+-cyclen) complexes (Zn2L1, Zn2L2, and Zn2L3), Cu2+, and Bar derivatives containing amino acid residues. We present successful formation of these artificial AP mimics with respect to the kinetics of the MNP hydrolysis obeying Michaelis–Menten scheme in aqueous solution and a two-phase solvent system and to the mode of the product inhibition by inorganic phosphate.
Highlights
The regulation of protein phosphorylation and dephosphorylation is an important process in terms of cellular signal transduction, apoptosis, and the cell cycle among other issues
Some artificial phosphatases that mimic the active center of metallophosphatases have been reported [11,12,13,14,15,16,17,18,19,20,21,22], very few of them function as catalysts for the hydrolysis of a phosphate monoester such as mono(4-nitrophenyl) phosphate (MNP)
We previously reported on the formation of the supramolecular complex 8a, by the 2:2:2 assembly of a bis(Zn2+-cyclen) complex containing 2,2 -bipyridyl linker 1 (Zn2L1), a dianion of barbital 4a (Bar), and a copper(II) ion in an aqueous solution which is stabilized by non-covalent bonds (Scheme 1a) [19,24]
Summary
The regulation of protein phosphorylation and dephosphorylation is an important process in terms of cellular signal transduction, apoptosis, and the cell cycle among other issues. The synthesis of artificial enzyme models that are constructed by covalent bonds require long and complex synthetic routes especially for their functionalization, as a result, only a limited number of structures have been reported These drawbacks, could be overcome by a supramolecular strategy utilizing the self-assembly of the artificial and functionalized molecular building blocks that are readily available [24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52]. Oroptatitciaolnrsowtaetiroenms ewaesrueremdewasiuthreadJwAiStCh Oa -JPA-S1C03O0-Pd-ig10it3a0l pdoiglaitrailmpeotlearriinm5e0temr imn 5c0elmlsmuscienlglsthuesinDglitnhee oDf lsiondeioufmso(d58iu9mnm(5)8.9Tnhmin)-.laTyheirn-clhayroemr cahtorogmraapthoygr(aTpLhCy)(TanLdC)sialnicda sgileilcacogleulmconlucmhrnomchartoomgraatpohgyrapwhays wpearsfopremrfeodrmuseidnguMsinergckMSeilriccka gSeillic6a0 gFe2l5460plFa2te54orpFlautjei SoilryFsiuajiCShielymsiicaalCChHemRiOcaMl ACTHORROEMXANTHO-RTLECX NPRHA-TTLEC, PanRdATFEu,jai nSdilFyusijai SiClyhseima CichalemFiLc-a1l0F0LD-10o0rDFourjiFuSjiilSyisliyasiaChCehmemiciaclalCCHHRROOMMAATTOORREEXX NNHH cchhrroommaattooggrraapphhyy SSiilliiccaa GGeell,, rreessppeeccttiivveellyy
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