A novel catalytic property of penicillin G amidase (PGA) is described. Unexpectedly, the enzyme can hydrolyse hydrazide bonds with good efficiency, and in solution the enzyme shows a selectivity that is similar to phenylacetamides. The hydrolysis of phenylacetic hydrazides releases hydrazine, but no inhibition due to the formation of such reactive compounds was observed. This novel catalytic property was assayed also on a solid phase as a pioneering route for the design of enzyme-cleavable linkers and masked scavengers for ketones. On a solid phase a phenylacetic hydrazide compound was chemically synthesised on PEGA1900 and PEGAþ (two co-polymers of acrylamide and ethylene glycol) and the efficiency of PGA in the release of phenylacetic acid depended on the diffusion of the protein inside the polymer. On PEGAþ the enzyme, as previously described, shows a good diffusion due to an improved electrostatic interaction with PGA thus achieving good hydrolytic conversions.

Penicillin G amidase catalysed hydrolysis of phenylacetic hydrazides: a new route to the solid phase chemoenzymatic synthesis and design of enzyme cleavable linkers

BASSO, ALESSANDRA;EBERT, CYNTHIA;GARDOSSI, Lucia;LINDA, PAOLO;
2005

Abstract

A novel catalytic property of penicillin G amidase (PGA) is described. Unexpectedly, the enzyme can hydrolyse hydrazide bonds with good efficiency, and in solution the enzyme shows a selectivity that is similar to phenylacetamides. The hydrolysis of phenylacetic hydrazides releases hydrazine, but no inhibition due to the formation of such reactive compounds was observed. This novel catalytic property was assayed also on a solid phase as a pioneering route for the design of enzyme-cleavable linkers and masked scavengers for ketones. On a solid phase a phenylacetic hydrazide compound was chemically synthesised on PEGA1900 and PEGAþ (two co-polymers of acrylamide and ethylene glycol) and the efficiency of PGA in the release of phenylacetic acid depended on the diffusion of the protein inside the polymer. On PEGAþ the enzyme, as previously described, shows a good diffusion due to an improved electrostatic interaction with PGA thus achieving good hydrolytic conversions.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11368/1694940
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