Linked Life Data

21329731

Source:http://linkedlifedata.com/resource/pubmed/id/21329731

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2-3
pubmed:dateCreated
2011-4-4
pubmed:abstractText
PEGylation and albumin binding are viewed as the most effective ways of prolonging the lifespans of short-lived peptides by delaying renal filtration. Here, we describe a derivative of exendin-4 with pharmaceutical benefits produced using both techniques. This exendin-4 derivative is based on a 4-arm PEG(20k) conjugated with two exendin-4s and two palmitylamines on its arms. PEG and palmitylamine were chosen to increase molecular size and bind to albumin, respectively. This derivative (Ex4-PEG-C16) was found to have larger molecular size (169kDa) than actual (28.9kDa) by size-exclusion chromatography and acceptable binding capability (~90%) to immobilized-albumin. Although the receptor-binding of Ex4-PEG-C16 to RIN-m5F cells was significantly lower than that of exendin-4, its acute anti-hyperglycemic efficacy was equivalent to that of exendin-4 in type 2 diabetic db/db mice. Furthermore, Ex4-PEG-C16 displayed a >6-fold increase in AUC and circulating t(1/2)vs. exendin-4. Due to this improvement, its hypoglycemic duration was greatly increased to 18.6h at a dose 250nmol/kg as compared with exendin-4 (8.7h). Our results show that the combined technique of PEGylation and albumin binding was effective when applied to exendin-4. We believe that this exendin-4 derivative has considerable pharmaceutical potential as a novel type 2 anti-diabetic systemic treatment.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1873-1686
pubmed:author
pubmed:copyrightInfo
2011 Elsevier B.V. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
11
pubmed:volume
167
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
239-45
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
A 4-arm polyethylene glycol derivative conjugated with exendin-4 peptide and palmitylamine having dual-function of size-increase and albumin-binding for long hypoglycemic action.
pubmed:affiliation
College of Pharmacy, Pusan National University, Jangjun-dong, Geumjeong-gu, Busan 609-735, Republic of Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't