Exploiting enzymatic (reversed) hydrolysis in directed self-assembly of peptide nanostructures

Enzyme-catalyzed reactions can be exploited to control molecular selfassembly under physiological conditions by converting nonassembling precursors into self-assembly building blocks. Two complementary approaches based on aromatic short-peptide derivatives that form molecular hydrogels are demonstrated. Firstly, it is shown that esterasedirected self assembly via hydrolysis of hydrophobic N-(fluorenyl-9methoxycarbonyl) (Fmoc)-peptide methyl esters give rise to formation of transparent hydrogels composed of defined peptide nanotubes. The internal and external diameters of these tubes are highly tunable, depending on the amino acid composition and chain length of the building blocks. Secondly, protease-directed self-assembly of Fmocpeptide esters is achieved via amide-bond formation (reversed hydrolysis) for combinations of Fmoc-threonine and leucine/phenylalanine methyl esters, producing fibrous hydrogels. Upon treatment with an esterase, these systems revert back to solution, thus providing a two-stage sohttion-gel-solution transition. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA.