Efficacy of native and hyperglycosylated follicle-stimulating hormone analogs for promoting fertility in female mice

Trousdale, Rhonda K.; Yu, Bo; Pollak, Susan; Husami, Nabil; Vidali, Andrea; Lustbader, Joyce W.

doi:10.1016/j.fertnstert.2007.11.013

Cited by 20 publications

(16 citation statements)

References 26 publications

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“…Expanding on this concept several studies have shown that increasing the number of sialic acid containing glycans beyond those of the native protein through engineered hyperglycosylation can effectively be employed as a technology to further optimize the circulatory half-life and in vivo activity of proteins. (24, 27, 206–208) Examples of pharmaceutically relevant proteins whose circulatory half-lifes were shown to be increased by hyperglycosylation include: interferon alfa and gamma,(26, 120) luteinizing hormone,(149) Fv antibody fragments,(209) asparaginase,(210, 211) cholinesterase,(164, 165) darbepoetin alfa (AraNESP ® ; Amgen),(25, 27, 161, 212–214) trombopoietin,(25, 27, 215) leptin,(25, 27) FSH,(159, 184, 216, 217) IFN-α2,(26) serum albumin,(145) and corifollitropin alfa. (218–222) Engineered glycosylation has been also employed to further optimize the in vivo pharmacological behavior of protein drugs by allowing for targeted delivery to disease-affected tissues.…”

Section: Optimization Of Protein Therapeutic Efficacy By Glycosylamentioning

confidence: 99%

Glycosylation of Therapeutic Proteins

2010

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During their development and administration, protein-based drugs routinely display suboptimum therapeutic efficacies due to their poor physicochemical and pharmacological properties. These innate liabilities have driven the development of molecular level strategies to improve the therapeutic behavior of protein drugs. Among, the currently developed approaches, glycoengineering is one of the most promising due fact that it has been shown to simultaneously afford improvements over most of the parameters necessary for optimization of protein drug in vivo efficacy (e.g., in vitro and in vivo molecular stability, pharmacodynamic responses, and pharmacokinetic profiles) while allowing for targeting to the desired site of action. The intent of this article is to provide an account of the effects that glycosylation has on the therapeutic efficacy of protein drugs and to describe the current understanding of the mechanisms by which glycosylation leads to such effects.

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Section: Optimization Of Protein Therapeutic Efficacy By Glycosylamentioning

confidence: 99%

Glycosylation of Therapeutic Proteins

2010

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“…By engineering up to four extra N‐linked glycosylation consensus sites into the α‐subunit (fused to the β‐subunit), retention time was enhanced (Perlman et al. 2003; Trousdale et al. 2009).…”

Section: Recombinant Gonadotropin Productionmentioning

confidence: 99%

“…By engineering up to four extra N-linked glycosylation consensus sites into the a-subunit (fused to the b-subunit), retention time was enhanced (Perlman et al 2003;Trousdale et al 2009). Increased retention time has also been achieved by adding a section of DNA that codes for a highly glycosylated protein to one terminus of the protein, the most common of these being the CTP of hCG.…”

Section: Recombinant Gonadotropin Productionmentioning

confidence: 99%

Advances in Recombinant Gonadotropin Production for Use in Bovine Superovulation

Hesser

Morris

Gibbons

2011

Reprod Domestic Animals

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Bovine ovarian hyperstimulation is a process that currently relies on pituitary-derived follicle stimulating hormone (FSH) to facilitate the maturation of multiple follicles to achieve dominance and eventual ovulation. The prevalence of this process, also called superovulation, has more than doubled in the past 10 years, but the efficiency of recovered transferable embryos has remained low at ~6 per collection. The use of pituitary-derived products presents other problems including contamination from other hormones, inconsistencies within and among batches, and the possibility of the spread of disease-transmitting agents. Recombinant gonadotropins have been engineered to yield varieties of FSH and luteinizing hormone from a myriad of heterologous hosts with the resulting products demonstrating various levels of biological activity. Research has also been devoted to alternative delivery methods to reduce the frequency of injections required in current superovulatory protocols. Together, recombinant gonadotropins and alternative delivery approaches potentially provide an economical alternative to the use of pituitary-derived products.

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“…Studies with highly purified natural isoforms of known glycan structure will undoubtedly provide useful insights not only into the physiological role of gonadotropin microheterogeneity but also on its importance in determining different efficacies of the hormone to activate distinct cellular signaling pathways. In the same line, it is also equally important to search into potential biased agonist effects of new gonadotropin glycosylation analogs created using recombinant DNA technology, such as hyperglycosylated FSH [162] and single-chain FSH analogs containing variable numbers of additional N-or O-linked carbohydrates [163], employing a palette of different read-outs. This approach may unveil unsuspected effects of these experimental analogs on selective signaling pathways triggered by the activated receptor, which may eventually help to predict unwanted side-effects when translated to the clinical arena.…”

Section: Glycan Structures In Gonadotropins and Their Role In Signal mentioning

confidence: 99%

Novel pathways in gonadotropin receptor signaling and biased agonism

Ulloa‐Aguirre

Crépieux

Poupon

et al. 2011

Rev Endocr Metab Disord

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Gonadotropins play a central role in the control of male and female reproduction. Selective agonists and antagonists of gonadotropin receptors would be of great interest for the treatment of infertility or as non steroidal contraceptive. However, to date, only native hormones are being used in assisted reproduction technologies as there is no pharmacological agent available to manipulate gonadotropin receptors. Over the last decade, there has been a growing perception of the complexity associated with gonadotropin receptors' cellular signaling. It is now clear that the Gs/cAMP/PKA pathway is not the sole mechanism that must be taken into account in order to understand these hormones' biological actions. In parallel, consistent with the emerging paradigm of biased agonism, several examples of ligand-mediated selective signaling pathway activation by gonadotropin receptors have been reported. Small molecule ligands, modulating antibodies interacting with the hormones and glycosylation variants of the native glycoproteins have all demonstrated their potential to trigger such selective signaling. Altogether, the available data and emerging concepts give rise to intriguing opportunities towards a more efficient control of reproductive function and associated disorders.

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Efficacy of native and hyperglycosylated follicle-stimulating hormone analogs for promoting fertility in female mice

Cited by 20 publications

References 26 publications

Glycosylation of Therapeutic Proteins

Glycosylation of Therapeutic Proteins

Advances in Recombinant Gonadotropin Production for Use in Bovine Superovulation

Novel pathways in gonadotropin receptor signaling and biased agonism

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