| Cobalt(III)-induced hexamerization of PEGylated insulin. | |
| | |
MedLine Citation:
|
PMID: 21835194 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
Insulin conjugates in which the B1Phe residue has been chemically modified often exhibit a reduced tendency to associate into hexamers due to weakened interactions between subunits. The purpose of this study was to prepare a hexamer formulation for such insulin conjugates by using Co(III) as a coordinating metal ion. PEGylated insulin in which monomethoxypoly(ethylene glycol) (mPEG, M(r) 5000 or 20,000) had been site-specifically attached to B1Phe was chosen as a model conjugate. Hexamerization of mPEG-insulin upon H(2)O(2)-mediated oxidation of Co(II) was kinetically and quantitatively analysed by visible spectrometry and size-exclusion HPLC. Co(III) mPEG-insulin hexamers thus obtained were extremely stable, existing mostly as a hexameric form even at nanomolar concentrations. A remarkable increase in hydrodynamic volumes was observed for Co(III) mPEG(20k)-insulin hexamers (1600kDa), as well as Co(III) mPEG(5k)-insulin hexamers (300kDa). Our results demonstrate the potential benefits of Co(III) hexamer formulation for weakly associating insulin conjugates in the treatment of diabetes. |
| | |
Authors:
|
Sung In Lim; Myung Hyun Jang; Dae Jin Kim; Sung Min Bae; Se Chang Kwon |
Related Documents
:
|
3534514 - Glucose intolerance in friedreich's ataxia: association with insulin resistance and dec... 3036804 - Stimulation of insulin-like growth factor ii receptor binding and insulin receptor kina... 3534894 - Comparative effects of several simple carbohydrates on erythrocyte insulin receptors in... 15094084 - Hippocampal synaptic plasticity and glutamate receptor regulation: influences of diabet... 16004854 - Patent foramen ovale: the never-ending story. 18280444 - Hemorheologic changes in type 2 diabetic patients with microangiopathic skin lesions. a... |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2011-8-3 |
Journal Detail:
|
Title: International journal of biological macromolecules Volume: - ISSN: 1879-0003 ISO Abbreviation: - Publication Date: 2011 Aug |
Date Detail:
|
Created Date: 2011-8-12 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 7909578 Medline TA: Int J Biol Macromol Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
|
Copyright © 2011 Elsevier B.V. All rights reserved. |
Affiliation:
|
Research Center, Hanmi Pharm. Co., Ltd., 377-1 Yeongcheon-ri, Dongtan-myeon, Hwaseong-si, Gyeonggi-do 445-813, Republic of Korea. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Mianserin, but not Ondansetron, reduces the locomotor stimulating effect of ethanol in preweanling r...
Next Document: Liver cirrhosis as a risk factor for mortality in a national cohort of patients with bacteremia.