Monoconjugation of Human Amylin with Methylpolyethyleneglycol
| Autor: | Priscilla Tinoco, Luís Maurício T.R. Lima, Tháyna Sisnande, Luiza C. S. Erthal, Raquel Rennó Braga, Luana Jotha-Mattos, Bruno Melo Vieira Gonçalves Ferreira, Luiz Henrique Guerreiro |
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| Rok vydání: | 2015 |
| Předmět: |
Blood Glucose
Male medicine.medical_specialty endocrine system endocrine system diseases medicine.medical_treatment Amylin lcsh:Medicine macromolecular substances Glucagon Polyethylene Glycols Mice Internal medicine medicine Cyclic AMP Glucose homeostasis Animals Homeostasis Humans Hypoglycemic Agents lcsh:Science Pancreatic hormone Multidisciplinary Chemistry Insulin lcsh:R Biological activity Islet Amyloid Polypeptide Kinetics Endocrinology Postprandial PEGylation MCF-7 Cells Solvents lcsh:Q Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 10, Iss 10, p e0138803 (2015) |
| ISSN: | 1932-6203 |
| Popis: | Amylin is a pancreatic hormone cosecreted with insulin that exerts unique roles in metabolism and glucose homeostasis. The therapeutic restoration of postprandial and basal amylin levels is highly desirable in diabetes mellitus. Protein conjugation with the biocompatible polymer polyethylene glycol (PEG) has been shown to extend the biological effects of biopharmaceuticals. We have designed a PEGylated human amylin by using the aminoreactive compound methoxylpolyethylene glycol succinimidyl carbonate (mPEGsc). The synthesis in organic solvent resulted in high yields of monoPEGylated human amylin, which showed large stability against aggregation, an 8 times increase in half-life in vivo compared to the non-conjugated amylin, and pharmacological activity as shown by modulation of cAMP production in MCF–7 cell line, decrease in glucagon and modulation of glycemia following subcutaneous administration in mice. Altogether these data reveal the potential use of PEGylated human amylin for the restoration of fasting amylin levels. |
| Databáze: | OpenAIRE |
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