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Monoconjugation of Human Amylin with Methylpolyethyleneglycol

Sisnande, Tháyna ; Guerreiro, Luiz Henrique ; Braga, Raquel R ; Jotha-Mattos, Luana ; Erthal, Luiza C S ; Tinoco, Priscilla ; Ferreira, Bruno M ; Lima, Luís Maurício T R Holscher, Christian

PloS one, 2015-10, Vol.10 (10), p.e0138803-e0138803 [Periódico revisado por pares]

United States: Public Library of Science

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Título:
Monoconjugation of Human Amylin with Methylpolyethyleneglycol
Autor: Sisnande, Tháyna ; Guerreiro, Luiz Henrique ; Braga, Raquel R ; Jotha-Mattos, Luana ; Erthal, Luiza C S ; Tinoco, Priscilla ; Ferreira, Bruno M ; Lima, Luís Maurício T R
Holscher, Christian
Assuntos: Amylin ; Animals ; Binding sites ; Biocompatibility ; Biological effects ; Biological products ; Blood glucose ; Blood Glucose - drug effects ; Carbonates ; Conjugation ; Cyclic AMP - metabolism ; Dextrose ; Diabetes ; Diabetes mellitus ; Epidemiology ; Fourier transforms ; Glucagon ; Glucagon - metabolism ; Glucose ; Glucose metabolism ; Health aspects ; Homeostasis ; Homeostasis - drug effects ; Humans ; Hypoglycemia ; Hypoglycemic Agents - chemistry ; Hypoglycemic Agents - pharmacology ; Insulin ; Islet Amyloid Polypeptide - chemistry ; Islet Amyloid Polypeptide - metabolism ; Islet Amyloid Polypeptide - pharmacology ; Kinetics ; Male ; MCF-7 Cells ; Metabolism ; Mice ; Modulation ; Pancreas ; Pharmacology ; Physiological aspects ; Polyethylene glycol ; Polyethylene Glycols - chemistry ; Polyethylene Glycols - pharmacology ; Polyols ; Polypeptides ; Restoration ; Solvents - chemistry
É parte de: PloS one, 2015-10, Vol.10 (10), p.e0138803-e0138803
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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Conceived and designed the experiments: TS LHG RRB LJM LCSE BMF LMTRL. Performed the experiments: TS LHG RRB LJM LCSE PT BMF LMTRL. Analyzed the data: TS LHG RRB LJM LCSE BMF LMTRL. Contributed reagents/materials/analysis tools: TS LHG RRB LJM LCSE BMF LMTRL. Wrote the paper: TS LHG LJM LCSE BMF LMTRL.
Competing Interests: Prof. Luis Mauricio T. R. Lima, Prof. Luiz H. Guerreiro and Dr. Bruno M. Ferreira are applicants of a patent regarding human amylin controlled release. "BIOCONJUGADOS NÃO AGLOMERANTES DE AMILINOMIMÉTICOS COM POLIETILENOGLICOL, USO DE BIOCONJUGADOS NÃO AGLOMERANTES DE AMILINOMIMÉTICOS COM POLIETILENOGLICOL, COMPOSIÇÕES FARMACÊUTICAS DE BAIXA TOXICIDADE, ADJUVANTE PARA A PREVENÇÃO OU TRATAMENTO DAS DOENÇAS, MEDICAMENTO, MÉTODO DE TRATAMENTO OU PREVENÇÃO DE DOENÇAS.” Luiz Henrique Guerreiro Rosado, Bruno Melo Ferreira, e Luís Mauricio T. R. Lima, BR10-2013-017626-5. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.
Descrição: 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.
Editor: United States: Public Library of Science
Idioma: Inglês

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Monoconjugation of Human Amylin with Methylpolyethyleneglycol

Sisnande, Tháyna ; Guerreiro, Luiz Henrique ; Braga, Raquel R ; Jotha-Mattos, Luana ; Erthal, Luiza C S ; Tinoco, Priscilla ; Ferreira, Bruno M ; Lima, Luís Maurício T R Holscher, Christian

United States: Public Library of Science

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