Peptide Fibril as a Stereoselective Glycosidase Mimic

The self-replicating materials can be useful models of understanding how molecular assemblies and cellular machineries emerged in the origin of life.¹ The steps from a simple chemical system to a formation of a fully functional living cell are numerous, and in order to investigate it we must start from the simplest autocatalytic system. Such system was developed previously by our group; self-replicating peptides that are able to accelerate their own formation.^2,3 Our group has reported a series of short peptides having the sequence (FE)_n or (EF)_n and bearing L-proline at their N- terminus that self-assembled into fibrillar networks and hydrogels.⁴ These networks have greater catalytic activity for the aldol reaction than their non-assembling analogues. So by insertion of catalytic group in to the self-replicating peptide we can couple both the replication and metabolic reactions into a single autocatalytic system. In order to achieve this, we have synthesized a self-replicating amphiphilic short peptide (5H) having alternate Glu-Phe units and a histidine catalytically active group at the 5^th position. This peptide has the ability to self-assemble in to β-sheets structure in water. This supramolecular superstructure can cleave glycosidase bonds of the model substrates. The peptide shows stereoselectivity in glycoside bond hydrolysis. It can cleave the β-glycosides more efficiently than the α-glycosides. This peptide has the greater catalytic activity than its non-aggregating analogue acetyl histidine.

References:

The origin of life: what we know,what we can know and what we will never know. Pascal, Addy Pross and Robert. 2013.
B. Rubinov, N. Wagner, M. Matmor, O. Regev, N. Ashkenasy, G. Ashkenasy. 2012, ACS Nano, Vol. 6, pp. 7893-7901.
B. Rubinov, N. Wagner, H. Rapaport, G. Ashkenasy. 2009, Angew. Chem., Vol. 121, pp. 6811-6814.
M. Tena-Solona, J. Nanda, S.-Diaz-Oltra, A. Chotera, G. Ashkenasy, B. Escudh. Chem. Eur.J. 2016, Vol. 22, pp. 6687-6694