[The molecular design and drug development of recombinant long-acting follicle stimulating hormone].
Follicle-stimulating hormone (FSH) is a glycoprotein which regulates the development, growth, pubertal maturation and reproductive processes of the body. Exogenous FSH has been used to promote ovarian follicular growth and maturation in female and spermatogenesis in male. The relative short elimination half life and rapid metabolic clearance of current versions of FSH require a daily or twice-daily scheduled subcutaneous injection to maintain stable FSH level being not below the threshold during ovarian stimulation. The development of recombinant long-acting FSH with enhanced biological activities may be helpful for less injection therefore to improve patient compliance, while reducing patient stress and error rates. A number of technological strategies have been explored to develop recombinant longer-acting FSH. For examples, attachment of the C-terminal peptide (CTP) of the human chorionic gonadotropin beta subunit or a sequence containing potential glycosylation sites to either subunit of FSH, creation of a single chain containing the alpha and beta subunits of FSH combined with CTP or N-linked glycosylation signal sequence as a linker, or fusion of the Fc domain of IgGi to FSH. Based on the modifiable molecular structure and pharmacokinetic and pharmacodynamic properties of recombinant FSH, it is hopeful that more FSH drugs with prolonged half-life and increased bioactivity will be developed to meet the modern clinical demands.
Institute of Molecular Medicine, Huaqiao University, Quanzhou 362021, China. diaoyong@hqu.edu.cn
Yong
Y
Diao
Jun-Sheng
JS
Lin
D000818:Animals; D043373:Follicle Stimulating Hormone, Human / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D006031:Glycosylation; D006207:Half-Life; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000737:chemistry / Q000378:metabolism; D010062:Ovulation Induction / Q000379:methods; D011962:Receptors, FSH / Q000737:chemistry / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D012098:Reproduction / Q000187:drug effects
D043373:Follicle Stimulating Hormone, Human; D007141:Immunoglobulin Fc Fragments; D011962:Receptors, FSH; D011993:Recombinant Fusion Proteins; C437186:follicle stimulating hormone, human, with HCG C-terminal peptide