Drug delivery systems employing 1,6-elimination: Releasable poly(ethylene glycol) conjugates of proteins

Citation
S. Lee et al., Drug delivery systems employing 1,6-elimination: Releasable poly(ethylene glycol) conjugates of proteins, BIOCONJ CHE, 12(2), 2001, pp. 163-169
Citations number
28
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOCONJUGATE CHEMISTRY
ISSN journal
1043-1802 → ACNP
Volume
12
Issue
2
Year of publication
2001
Pages
163 - 169
Database
ISI
SICI code
1043-1802(200103/04)12:2<163:DDSE1R>2.0.ZU;2-N
Abstract
Using lysozyme as a representative protein substrate that loses its activit y when PEGylation takes place on the epsilon -amino group of lysine residue s, various amounts of a novel releasable PEG linker (rPEG) were conjugated to the protein. rPEG-lysozyme conjugates were relatively stable in pH 7.4 b uffer for over 24 h. However, regeneration of native protein from the rPEG conjugates occurred in a predictable manner during incubation in high pH bu ffer or rat plasma, as demonstrated by enzymatic activity and structural ch aracterization. The rates of regeneration were also correlated with PEG num ber: native lysozyme was released more rapidly from the monosubstituted con jugate than from the disubstituted conjugate, suggesting possible steric hi ndrance to the approach of cleaving enzymes. Recovery of normal activity an d structure for the regenerated native lysozyme was shown by a variety of a ssays.