Abstract
We modified amylin chemically by conjugating methoxyl polyethyleneglycol succinimidyl carbonate (mPEGSC) of varying molecular weights (1 kDa, 2 kDa and 5 kDa). The reaction occurred within a few minutes, resulting in at least four distinct PEGylated products. The reaction products were separated by reversed-phase chromatography and identified by mass-spectrometry. The monoPEGylated and diPEGylated amylin products were generated rapidly through conjugation to the two amino groups of the N-terminal lysine residue. Both PEGylated amylin products bound to the receptor activity-modifying protein 1 (RAMP1). Pharmacological evaluation by subcutaneous administration in mice of monoPEGylated and diPEGylated amylin obtained with mPEG-SC 5 kDa revealed that both compounds modulated glycemia for longer times than unmodified amylin. Collectively, these data demonstrate the potential of bioconjugation with mPEG for the design of amylin therapeutics with sustained action.
Keywords: Amylin, diabetes, glycemia, islet associated polypeptide, PEGylation.
Protein & Peptide Letters
Title:Amylin Conjugation with Methoxyl Polyethyleneglycol
Volume: 20 Issue: 11
Author(s): Mariana F. A. N. Guterres, Luiz Henrique Guerreiro, Bruno Melo-Ferreira, Luiza C. S. Erthal and Luís Maurício T. R. Lima
Affiliation:
Keywords: Amylin, diabetes, glycemia, islet associated polypeptide, PEGylation.
Abstract: We modified amylin chemically by conjugating methoxyl polyethyleneglycol succinimidyl carbonate (mPEGSC) of varying molecular weights (1 kDa, 2 kDa and 5 kDa). The reaction occurred within a few minutes, resulting in at least four distinct PEGylated products. The reaction products were separated by reversed-phase chromatography and identified by mass-spectrometry. The monoPEGylated and diPEGylated amylin products were generated rapidly through conjugation to the two amino groups of the N-terminal lysine residue. Both PEGylated amylin products bound to the receptor activity-modifying protein 1 (RAMP1). Pharmacological evaluation by subcutaneous administration in mice of monoPEGylated and diPEGylated amylin obtained with mPEG-SC 5 kDa revealed that both compounds modulated glycemia for longer times than unmodified amylin. Collectively, these data demonstrate the potential of bioconjugation with mPEG for the design of amylin therapeutics with sustained action.
Export Options
About this article
Cite this article as:
F. A. N. Guterres Mariana, Guerreiro Henrique Luiz, Melo-Ferreira Bruno, S. Erthal C. Luiza and T. R. Lima Maurício Luís, Amylin Conjugation with Methoxyl Polyethyleneglycol, Protein & Peptide Letters 2013; 20 (11) . https://dx.doi.org/10.2174/09298665113209990067
DOI https://dx.doi.org/10.2174/09298665113209990067 |
Print ISSN 0929-8665 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5305 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Non-Vitamin K Oral Anticoagulant Drugs for Stroke Prevention in Patients with Atrial Fibrillation and Chronic Kidney Disease
Current Medicinal Chemistry Zinc and its Specific Transporters as Potential Targets in Airway Disease
Current Drug Targets Vitamin D-Binding Protein Acts in the Actin Scavenge System and Can Have Increased Expression During Aspirin Therapy
Current Neurovascular Research Multitasking of Neuropeptide Y through the Lens of Motifs
Recent Patents on CNS Drug Discovery (Discontinued) IGF-1R Inhibitor Ameliorates Diabetic Nephropathy with Suppressed HMGN1/TLR4 Pathway
Endocrine, Metabolic & Immune Disorders - Drug Targets Advanced Glycation End Products (AGEs), Oxidative Stress and Diabetic Retinopathy
Current Pharmaceutical Biotechnology Perspectives on Medicinal Properties of Mangiferin
Mini-Reviews in Medicinal Chemistry A Knock-Down Cell-Based Study for the Functional Analysis of Chloride Intracellular Channel 1 (CLIC1): Integrated Proteomics and Microarray Study
Protein & Peptide Letters Endothelin Receptors, Mitochondria and Neurogenesis in Cerebral Ischemia
Current Neuropharmacology Anti-VEGF Therapy for Retinal Vein Occlusions
Current Drug Targets Magnesium in Pain Research: State of the Art
Current Medicinal Chemistry Application of NMR Spectroscopy in Medicinal Chemistry and Drug Discovery
Current Topics in Medicinal Chemistry Design, Synthesis and Biological Evaluation of Antipicornaviral Pyrrole-Containing Peptidomimetics
Protein & Peptide Letters Treating Cancer and No-Cancer Pain in Older and Oldest Old Patients
Current Pharmaceutical Design Impact of Red Wine Consumption on Cardiovascular Health
Current Medicinal Chemistry The Therapeutic Potential of Allosteric Ligands for Free Fatty Acid Sensitive GPCRs
Current Topics in Medicinal Chemistry Study of Male Sex Hormone Levels in Male Egyptian Children with Beta-Thalassemia: Correlation with Iron load
Endocrine, Metabolic & Immune Disorders - Drug Targets Circulating Nucleic Acids in Plasma and Serum: Roles in Diagnosis and Prognosis in Diabetes and Cancer
Infectious Disorders - Drug Targets Role of Iron Deficiency and Overload in the Pathogenesis of Diabetes and Diabetic Complications
Current Medicinal Chemistry <i>Prunella vulgaris</i> L: Critical Pharmacological, Expository Traditional Uses and Extensive Phytochemistry: A Review
Current Drug Discovery Technologies