Carbohydrate composition and site-occupancy determination in pituitary and recombinant preparations of human thyrotropin
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2017
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Journal of Biotechnology
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Human thyrotropin (hTSH) is a glycoprotein with three potential
glycosylation sites: two in the -subunit and one in the
-subunit. Carbohydrate site-occupancy is frequently neglected in
glycoprotein characterization, even if related to folding, trafficking,
initiation of inflammation, host defence and congenital disorders
of glycosylation (CDG). For the first-time N-glycoprofiling analysis
was applied to site-occupancy determination of two native pituitary
hTSH, in comparison with three CHO-derived preparations
of hTSH, a widely used biopharmaceutical. A single methodology
provided: (i) average N-glycan mass; (ii) mass fraction of
each monosaccharide and of sulfate; (iii) percent carbohydrate.
The results indicate that occupancy (65–87%) and carbohydrate
mass (12–19%) can be 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). The number of moles of fucose per mole of hTSH was
found 2.5-fold higher in the pituitary preparations. One of these
native preparations, presenting the smallest glycan mass, lowest
occupancy, GalNAc, sulfate, Gal and sialic acid contents, also presented
the lowest in vivo bioactivity and circulatory half-life. This
methodology, extremely important for comparing a recombinant
biopharmaceutical to its native equivalent, can be applied to any
physiologically or clinical relevant glycoprotein.
Como referenciar
BARTOLINI, PAOLO; 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. Carbohydrate composition and site-occupancy determination in pituitary and recombinant preparations of human thyrotropin. Journal of Biotechnology, v. 256, p. S15-S15, 2017. suppl.. DOI: 10.1016/j.jbiotec.2017.06.053. Disponível em: http://repositorio.ipen.br/handle/123456789/28652. 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.