Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.3.1.108 (
TAT
)
2,389
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
To improve the pharmacological properties of maize ribosome-inactivating protein (maize RIP) for targeting HIV-infected cells, the previously engineered
TAT
-fused active form of maize RIP (
MOD
) was further engineered for cysteine-directed PEGylation. In this work, two potential antigenic sites, namely Lys-78 and Lys-264, were identified. They were mutated to cysteine residue and conjugated with PEG
5k
or PEG
20k
. The resultant PEG derivatives of
MOD
variants were examined for ribosome-inactivating activity, circulating half-life and immunogenicity. Our results showed that
MOD
-PEG conjugates had two- to five-fold lower biological activity compared to the wild-type. Mutation of the two sites respectively did not decrease the anti-
MOD
IgG and IgE level in mice, but the conjugation of PEG did dramatically reduce the antigenicity. Furthermore, pharmacokinetics studies demonstrated that attachment of PEG
20k
prolonged the plasma half-life by five-fold for
MOD
-K78C and 17-fold for
MOD
-K264C, respectively. The site-specific mutation together with PEGylation therefore generated
MOD
derivatives with improved pharmacological properties.
...
PMID:Improvement of the Pharmacological Properties of Maize RIP by Cysteine-Specific PEGylation. 2776 6
