Abstract:
BACKGROUND:Glucagon is a peptide hormone with many uses as a therapeutic agent, including the emergency treatment of hypoglycemia. Physical instability of glucagon in solution leads to problems with the manufacture, formulation, and delivery of this pharmaceutical product. Glucagon has been shown to aggregate and form fibrils and gels in vitro. Small oligomeric precursors serve to initiate and nucleate the aggregation process. In this study, these initial aggregates, or seed nuclei, are characterized in bulk solution using light scattering methods and field-flow fractionation. RESULTS:High molecular weight aggregates of glucagon were detected in otherwise monomeric solutions using light scattering techniques. These aggregates were detected upon initial mixing of glucagon powder in dilute HCl and NaOH. In the pharmaceutically relevant case of acidic glucagon, the removal of aggregates by filtration significantly slowed the aggregation process. Field-flow fractionation was used to separate aggregates from monomeric glucagon and determine relative mass. The molar mass of the large aggregates was shown to grow appreciably over time as the glucagon solutions gelled. CONCLUSION:The results of this study indicate that initial glucagon solutions are predominantly monomeric, but contain small quantities of large aggregates. These results suggest that the initial aggregates are seed nuclei, or intermediates which catalyze the aggregation process, even at low concentrations.
journal_name
J Biol Engjournal_title
Journal of biological engineeringauthors
Hoppe CC,Nguyen LT,Kirsch LE,Wiencek JMdoi
10.1186/1754-1611-2-10subject
Has Abstractpub_date
2008-07-09 00:00:00pages
10issn
1754-1611pii
1754-1611-2-10journal_volume
2pub_type
杂志文章abstract::An intestinal protozoan parasite, Cryptosporidium parvum, is a major cause of waterborne gastrointestinal disease worldwide. Detection of Cryptosporidium oocysts in potable water is a high priority for the water treatment industry to reduce potential outbreaks among the consumer populace. Anti-Cryptosporidium oocyst p...
journal_title:Journal of biological engineering
pub_type: 杂志文章
doi:10.1186/1754-1611-1-3
更新日期:2007-10-10 00:00:00
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journal_title:Journal of biological engineering
pub_type: 杂志文章
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更新日期:2018-12-04 00:00:00
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journal_title:Journal of biological engineering
pub_type: 杂志文章
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更新日期:2019-10-29 00:00:00
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journal_title:Journal of biological engineering
pub_type: 杂志文章
doi:10.1186/1754-1611-6-22
更新日期:2012-11-13 00:00:00
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journal_title:Journal of biological engineering
pub_type: 杂志文章
doi:10.1186/1754-1611-3-1
更新日期:2009-01-02 00:00:00
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journal_title:Journal of biological engineering
pub_type: 杂志文章,评审
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更新日期:2020-03-13 00:00:00
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journal_title:Journal of biological engineering
pub_type: 杂志文章
doi:10.1186/1754-1611-6-1
更新日期:2012-02-28 00:00:00
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journal_title:Journal of biological engineering
pub_type: 杂志文章,评审
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更新日期:2017-12-13 00:00:00
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journal_title:Journal of biological engineering
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doi:10.1186/s13036-018-0116-5
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pub_type: 杂志文章,评审
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更新日期:2020-09-09 00:00:00
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journal_title:Journal of biological engineering
pub_type: 杂志文章,评审
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更新日期:2017-09-01 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2020-05-06 00:00:00
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journal_title:Journal of biological engineering
pub_type: 杂志文章
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更新日期:2010-06-09 00:00:00
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journal_title:Journal of biological engineering
pub_type: 杂志文章,评审
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更新日期:2019-01-18 00:00:00
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journal_title:Journal of biological engineering
pub_type: 杂志文章
doi:10.1186/1754-1611-5-12
更新日期:2011-09-20 00:00:00
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journal_title:Journal of biological engineering
pub_type: 杂志文章
doi:10.1186/s13036-017-0062-7
更新日期:2017-11-21 00:00:00
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journal_title:Journal of biological engineering
pub_type: 杂志文章
doi:10.1186/1754-1611-8-15
更新日期:2014-07-01 00:00:00
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journal_title:Journal of biological engineering
pub_type: 杂志文章,评审
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更新日期:2019-01-09 00:00:00
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journal_title:Journal of biological engineering
pub_type: 杂志文章
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更新日期:2013-12-02 00:00:00
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journal_title:Journal of biological engineering
pub_type: 杂志文章,评审
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更新日期:2019-02-19 00:00:00
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journal_title:Journal of biological engineering
pub_type: 杂志文章
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更新日期:2019-06-28 00:00:00
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journal_title:Journal of biological engineering
pub_type: 杂志文章,评审
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更新日期:2017-06-29 00:00:00
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journal_title:Journal of biological engineering
pub_type: 杂志文章
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更新日期:2017-07-12 00:00:00
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journal_title:Journal of biological engineering
pub_type: 杂志文章
doi:10.1186/1754-1611-6-19
更新日期:2012-10-10 00:00:00
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journal_title:Journal of biological engineering
pub_type: 杂志文章
doi:10.1186/s13036-019-0163-6
更新日期:2019-05-30 00:00:00
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journal_title:Journal of biological engineering
pub_type: 杂志文章
doi:10.1186/1754-1611-6-18
更新日期:2012-09-14 00:00:00
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journal_title:Journal of biological engineering
pub_type: 杂志文章
doi:10.1186/1754-1611-6-6
更新日期:2012-05-15 00:00:00
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journal_title:Journal of biological engineering
pub_type: 杂志文章
doi:10.1186/s13036-017-0084-1
更新日期:2017-11-02 00:00:00