期刊
MOLECULAR PHARMACEUTICS
卷 10, 期 5, 页码 2054-2061出版社
AMER CHEMICAL SOC
DOI: 10.1021/mp4000629
关键词
agglutinin; glycoprotein; glycosylation; haemagglutination; lectin; PEGylation
资金
- EC research program GlycoHIT [260600]
- RTN network GLYCOPHARM [317297]
- Charles University [PRVOUK-27]
- Verein zur Forderung des biologisch-technologischen Fortschritts in der Medizin e. V. (Heidelberg, Germany)
The emerging insights into the physiological significance of endogenous lectins prompted us to characterize the effect of monosubstitution with poly(ethylene glycol) (PEG; 5 kDa) on a human lectin. As role model, we used a member of the galectin family, that is, galectin-2, the Cys57Met (single-site) mutant and its monoPEGylated derivative. The activities of these three proteins were comparatively studied by biochemical, cell biological, and histochemical methods, using surface-immobilized glycoproteins, different types of cells presenting gangliosides or (glyco)proteins as counterreceptors in vitro and tissue sections. PEGylation led to decreases in affinity/signal intensity with context dependence. The introduction of the mutation, too, can influence reactivity. Assays on haemagglutination and inhibition of cell proliferation underscored that mutational engineering and substitution can (but must not necessarily) affect this protein's activity. Serum clearance in rats was markedly retarded by PEGylation. Overall, the bulky substitution, spatially comparable to N-glycans, can markedly reduce binding of the galectin to physiological binding sites.
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