Advanced search
Start date
Betweenand

Synthesis and characterization of different glycoforms of recombinant human thyrotropin (rhTSH) pharmacologically actives

Abstract

Recombinant human thyrotropin (rhTSH) is a glycohormone of great medical interest, widely used in diagnosis and therapy of thyroid cancer, because it maintains the quality of life of patients in this condition and who otherwise would be left in hypothyroid condition, with a very poor quality of life. Unfortunately there is only one company in the world selling, at an exorbitant price, rhTSH. We emphasize that our Research Group has already synthesized rhTSH in CHO cells and later a "humanized" form of this hormone, with a Patent deposit in both case. In the synthesis of therapeutic glycoproteins in CHO cells, the understanding of aspects of the process of cell culture that reflect the control of the resultant glycosylation is extremely important to ensure products with defined bioactivity and pharmacological properties. This especially considering that the biological activity and hence the physiological and pharmacological action of glycoproteins are highly dependent on their glicidic portion, i.e. on the structure and quantity of oligosaccharides (glycans) attached to them. In this project, our aim is to study the percentage of occupancy of the glycosylation sites (i.e. how many, in the average, of the three N-glycosylation sites of hTSH molecule are occupied), the quality and quantity of the specific structures of N-glycans and the level of sialylation of hTSH preparations with different glycoforms. These preparations will be obtained adding some compounds (ions and organic molecules) used in the cultivation of CHO cells that can cause changes in glycosylation profile. Therefore, we will study the effects on r-hTSH glycosylation of Mn +2, sodium butyrate and cycloheximide, individually or in combination, in comparison with the natural, pituitary hormone and with the traditional recombinant product (ThyrogenR). It is worth to emphasise that even the glicidic structures of natural hormone and of traditional recombinant hTSH are very little known and studied. This type of study is extremely important, both from the point of view of the development of new biopharmaceuticals and of the quality control of glycoprotein hormones already used in clinical applications. (AU)

Articles published in Agência FAPESP Newsletter about the research grant:
Articles published in other media outlets (0 total):
More itemsLess items
VEICULO: TITULO (DATA)
VEICULO: TITULO (DATA)

Scientific publications (4)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
ALMEIDA, B. E.; OLIVEIRA, J. E.; DAMIANI, R.; DALMORA, S. L.; BARTOLINI, P.; RIBELA, M. T. C. P.. Qualitative and quantitative reversed-phase high performance liquid chromatographic analysis of glycoprotein hormones in the presence of a large excess of human serum albumin. Journal of Pharmaceutical and Biomedical Analysis, v. 63, p. 160-164, . (11/07289-0)
ALMEIDA, B. E.; DAMIANI, R.; OLIVEIRA, J. E.; DALMORA, S. L.; TORJESEN, P. A.; BARTOLINI, P.; RIBELA, M. T. C. P.. Reversed-phase high performance liquid chromatography as an alternative to animal bioassay for human thyrotropin potency determination. ANALYTICAL METHODS, v. 6, n. 17, p. 6688-6694, . (11/07289-0)
DAMIANI, RENATA; ALMEIDA, BEATRIZ E.; OLIVEIRA, JOAO E.; BARTOLINI, PAOLO; RIBELA, MARIA TERESA C. P.. Enhancement of Human Thyrotropin Synthesis by Sodium Butyrate Addition to Serum-Free CHO Cell Culture. Applied Biochemistry and Biotechnology, v. 171, n. 7, p. 1658-1672, . (11/07289-0)
RIBELA, MARIA TERESA 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. 2, . (15/26058-0, 11/07289-0, 12/10779-2)

Please report errors in scientific publications list by writing to: cdi@fapesp.br.