ArticleInternational journal of clinical and experimental medicine2015
A noncytolytic antibody-like extendin-4-IgG4 fusion protein as a long-acting potential anti-diabetic agent.
Article in International journal of clinical and experimental medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed, 1 citations in OpenAlex.
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13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGLP-1 and its analogs have a variety of anti-diabetic effects. However, short half-life and rapid degraded by DPP-IV limits the therapeutic potential of the native GLP-1. So, many DPP-IV-resistant and long-acting GLP-1 analogs were developed. In this study, an antibody-like extendin-4-IgG4 fusion protein was developed.
methodsThe γ4 constant region contains two amino acid substitutions relative to native γ4 (S228P and L235E) lead to affinity for FcγRI to be low and stability of the IgG4 molecular. The fusion protein was expressed in CHO cells and assembled into an immunoglobulin-like structure with molecular weight of approximately 130 kDa.
resultsThe Exendin-4-IgG4 fusion protein was found to affinity bind GLP-1R in vitro. In vivo when compared the potency and duration of glucose-lowering effects in diabetic (db/db) mice at the same dose, exendin-4 resulted in a glucose-lowering effect that persisted only for 6 hours, but the extendin-4-IgG4 fusion protein for more than 168 hours. Injecting subcutaneously with a high dose of the fusion protein led normal BALB/c mice to the lower blood glucose level but did not cause serious hypoglycemia. Especially, the half-life time of the fusion protein in cynomolgus monkeys was about 180 hours, almost the longest half-life time among the developed GPL-1 analogues, which suggested a longer half-life time in human.
conclusionsThe intact antibody-like fusion protein has more advantages than the Fc fusion protein including the intent of prolonging the half-life. These results also suggested the fusion protein was a safe and long-acting potential anti-diabetic agent.
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Identifiers
26064256PMC4443090W2410171183What OpenQuestion holds
Registered trials
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