Design and synthesis of libraries of artificial enzymes
|Justyna Majchrzak , Justyna Frączyk , Zbigniew J. Kamiński , Beata Kolesińska|
Technical University of Łódź, Institute of Organic Chemistry (PŁ), Żeromskiego 116, Łódź 90-924, Poland
Based on the observation that process of binding ligands by artificial receptors formed be self-organisation of N-lipidated peptides immobilized on the cellulose is reversible we designed catalytically active structures by incorporation into the peptide fragment amino acids sequences characteristic for enzymatic active sites. Designing the catalytic structure we learned lesson from Nature, expecting several advantages arisen from positioning of the substrate inside of the binding pocked of catalytically active moiety. We expected, that contrary to the most of man-made catalysts designed in accord to the concept of close contact of the substrates located in the outside of catalytically active core structure, catalytic monolayer of N-lipidated peptides immobilized on cellulose via triazine scaffold would act much more efficiently and selectively, resembling enzymes. In the consequence of this conceptual approach, the catalytic processes may proceeds in the most suitable microenvironment, under milder conditions, much faster and with exceedingly high regio-, chemo-, and stereoselectivity.
Catalyst were prepared  by self organization of podands prepared from N-lipidated oligopeptides tethered in the regular fashion to the cellulose via linker made from fenylenediamine and 2,4-dichloro-6-methoxy-1,3,5-triazine. For assembling of the all elements of the podands, triazine coupling reagents were used  in all coupling steps.
The library of highly potent artificial esterases was prepared by incorporation into the peptide fragment residues of catalytic triade His, Ser, Asp (Glu). The activity of catalysts has been confirmed by hydrolysis and alcoholysis of p-nitrophenyl esters of N-protected di- and tripeptides.
Recently, we found that general approach presented above can be applied also for designing the library of artificial isomerases catalyzing O→N (N→O) isomerisation of N-benzoyl-2-phenylisoserine , side chain of Paclitaxel and carboranes.
Acknowledgements: The study was supported by the Ministry of Science and High Education under the Research Project N N204 326737.
 a) Majchrzak, J.; Frączyk, J.; Kamiński, Z.J. Acta Poloniae Pharm. 65, 703-708 (2008); b) Fraczyk, J.; Kaminski, Z.J. J. Comb. Chem. 10, 934-940 (2008).
 Kamiński, Z. J.; Kolesińska, B.; Kolesińska, J.; Sabatino, G.; Chelli, M.; Rovero, P.; Błaszczyk, M.; Główka, M. L.; Papini, A. M. J. Am. Chem. Soc., 127, 16912-16920 (2005).
Presentation: Poster at SMCBS'2009 International Workshop, by Justyna Majchrzak
See On-line Journal of SMCBS'2009 International Workshop
Submitted: 2009-09-07 13:50 Revised: 2009-09-07 13:50