title: Monoconjugation of Human Amylin with Methylpolyethyleneglycol.
abstract: 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.
authors.affiliation: Federal University of Rio de Janeiro-UFRJ, CCS, Bss24, Ilha do Fundão, 21941-590, Rio de Janeiro, RJ, Brazil.
authors.forename: Tháyna
authors.initials: T
authors.lastname: Sisnande
authors.affiliation: Department of Chemistry, Institute of Exact Sciences, Rural Federal University of Rio de Janeiro-Universidade Federal Rural do Rio de Janeiro, Rodovia BR 465, km 7, CEP: 23890-000, Seropédica, RJ, Brazil.
authors.forename: Luiz Henrique
authors.initials: LH
authors.lastname: Guerreiro
authors.affiliation: Federal University of Rio de Janeiro-UFRJ, CCS, Bss24, Ilha do Fundão, 21941-590, Rio de Janeiro, RJ, Brazil.
authors.forename: Raquel R
authors.initials: RR
authors.lastname: Braga
authors.affiliation: Federal University of Rio de Janeiro-UFRJ, CCS, Bss24, Ilha do Fundão, 21941-590, Rio de Janeiro, RJ, Brazil.
authors.forename: Luana
authors.initials: L
authors.lastname: Jotha-Mattos
authors.affiliation: Federal University of Rio de Janeiro-UFRJ, CCS, Bss24, Ilha do Fundão, 21941-590, Rio de Janeiro, RJ, Brazil.
authors.forename: Luiza C S
authors.initials: LC
authors.lastname: Erthal
authors.affiliation: Department of Chemistry, Institute of Exact Sciences, Rural Federal University of Rio de Janeiro-Universidade Federal Rural do Rio de Janeiro, Rodovia BR 465, km 7, CEP: 23890-000, Seropédica, RJ, Brazil.
authors.forename: Priscilla
authors.initials: P
authors.lastname: Tinoco
authors.affiliation: Federal University of Rio de Janeiro-UFRJ, CCS, Bss24, Ilha do Fundão, 21941-590, Rio de Janeiro, RJ, Brazil.
authors.forename: Bruno M
authors.initials: BM
authors.lastname: Ferreira
authors.affiliation: Federal University of Rio de Janeiro-UFRJ, CCS, Bss24, Ilha do Fundão, 21941-590, Rio de Janeiro, RJ, Brazil; Laboratory for Macromolecules (LAMAC-DIMAV), Brazilian National Institute of Metrology, Quality and Technology-INMETRO, Av. N. Sa. das Graças, 50-Xerém, Duque de Caxias-RJ, 25250-020, Rio de Janeiro, Brazil; National Institute of Science and Technology for Structural Biology and Bioimaging (INBEB-INCT), Federal University of Rio de Janeiro, Rio de Janeiro 21941-590, Brazil.
authors.forename: Luís Maurício T R
authors.initials: LM
authors.lastname: Lima
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D005934:Glucagon / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000494:pharmacology; D058228:Islet Amyloid Polypeptide / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D007700:Kinetics; D061986:MCF-7 Cells; D008297:Male; D051379:Mice; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000494:pharmacology; D012997:Solvents / Q000737:chemistry
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D058228:Islet Amyloid Polypeptide; D012997:Solvents; D011092:Polyethylene Glycols; D005934:Glucagon; D000242:Cyclic AMP