N-Glycoprofiling analysis for carbohydrate composition and site-occupancy determination in a poly-glycosylated protein: human thyrotropin of different origins
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2017
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International Journal of Molecular Sciences
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Human thyrotropin (hTSH) is a glycoprotein with three potential glycosylation sites: two in
the -subunit and one in the -subunit. These sites are not always occupied and occupancy is
frequently neglected in glycoprotein characterization, even though it is related to folding, trafficking,
initiation of inflammation and host defense, as well as congenital disorders of glycosylation (CDG).
For the first time N-glycoprofiling analysis was applied to the site-occupancy determination of
two native pituitary hTSH, in comparison with three recombinant preparations of hTSH, a widely
used biopharmaceutical. A single methodology provided the: (i) average N-glycan mass; (ii) mass
fraction of each monosaccharide and of sulfate; and (iii) percent carbohydrate. The results indicate
that the occupancy (65%–87%) and carbohydrate mass (12%–19%) can be up to 34%–57% higher in
recombinant hormones. The average glycan mass is 24% lower in pituitary hTSH and contains ~3-fold
fewer moles of galactose (p < 0.005) and sialic acid (p < 0.01). One of the two native preparations,
which had the smallest glycan mass together with the lowest occupancy and GalNAc, sulfate,
Gal and sialic acid contents, also presented the lowest in vivo bioactivity and circulatory half-life.
The methodology described, comparing a recombinant biopharmaceutical to its native equivalent,
can be applied to any physiologically or clinical relevant glycoprotein.
Como referenciar
RIBELA, MARIA T.C.P.; DAMIANI, RENATA; SILVA, FELIPE D.; LIMA, ELIANA R.; OLIVEIRA, JOAO E.; PERONI, CIBELE N.; TORJESEN, PETER A.; SOARES, CARLOS R.; BARTOLINI, PAOLO. N-Glycoprofiling analysis for carbohydrate composition and site-occupancy determination in a poly-glycosylated protein: human thyrotropin of different origins. International Journal of Molecular Sciences, v. 18, n. 131, p. 1-15, 2017. DOI: 10.3390/ijms18020131. Disponível em: http://repositorio.ipen.br/handle/123456789/27146. Acesso em: 20 Mar 2025.
Esta referência é gerada automaticamente de acordo com as normas do estilo IPEN/SP (ABNT NBR 6023) e recomenda-se uma verificação final e ajustes caso necessário.