Premium
Penicillin G Amidase‐Catalysed Hydrolysis of Phenylacetic Hydrazides on a Solid Phase: A New Route to Enzyme‐Cleavable Linkers
Author(s) -
Basso Alessandra,
Ebert Cynthia,
Gardossi Lucia,
Linda Paolo,
Tran Phuong Thao,
Zhu Mingzhao,
Wessjohann Ludger
Publication year - 2005
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.200505038
Subject(s) - chemistry , hydrazide , phenylacetic acid , penicillin amidase , hydrolysis , amidase , organic chemistry , polymer , oxime , hydroamination , combinatorial chemistry , catalysis , enzyme , polymer chemistry , immobilized enzyme
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 PEGA 1900 and PEGA + (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 PEGA + the enzyme, as previously described, shows a good diffusion due to an improved electrostatic interaction with PGA thus achieving good hydrolytic conversions.