Histaminase PEGylation: preparation and characterization of a new bioconjugate for therapeutic application.
Copper amine oxidase catalyses the oxidative deamination of primary amino groups of several biogenic amines, one of which is histamine, the principal chemical mediator of the first phase of allergic reactions. Looking forward to a possible future therapeutic application of this enzyme in the field of histamine-mediated afflictions, we developed a simple method for the purification of a histaminase from grass pea shoots, a source particularly enriched with the enzyme. Furthermore, in order to improve its therapeutic potential, in particular to reduce the high impurity due to its heterologous source, we conjugated the protein with poly(ethylene glycol) and tested the molecular, immunogenic and pharmacokinetic properties of the native and modified forms. The PEGylated enzyme showed molecular and enzymatic properties similar to those of the unmodified one, but the PEGylation extended the permanence of the injected drug in the body and eliminated its high immunogenic behaviour. The considerable ease of native histaminase production as well as the improved properties after PEGylation, make this engineered plant enzyme a suitable drug candidate for alternative treatment of histamine-mediated affections.
Federico
Rodolfo
R
Department of Biology, University of Roma Tre, Italy.
Cona
Alessandra
A
Caliceti
Paolo
P
Veronese
Francesco M
FM
D000465:Algorithms; D006631:Amine Oxidase (Copper-Containing) / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D005079:Excipients; D005456:Fluorescent Dyes; D006632:Histamine / Q000502:physiology; D007275:Injections, Intravenous; D027807:Lathyrus / Q000201:enzymology; D051379:Mice; D008807:Mice, Inbred BALB C; D011092:Polyethylene Glycols / Q000737:chemistry*
D005079:Excipients; D005456:Fluorescent Dyes; D011092:Polyethylene Glycols; D006632:Histamine; D006631:Amine Oxidase (Copper-Containing)