Linked Life Data

6372857

Source:http://linkedlifedata.com/resource/pubmed/id/6372857

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
1984-6-22
pubmed:abstractText
We report the synthesis of [2-glycine-A]insulin ([ Gly2 -A]insulin) and [2-alanine-A]insulin ([ Ala2-A]insulin) in which the indicated amino acid has been substituted for isoleucine found in this position in the natural hormone. The circular dichroic (CD) spectra of the analogues were obtained, and their properties were examined in several biological assays. CD studies suggested that the analogues remain monomeric at concentrations at which insulin is partly or mostly dimeric. Both analogues are extremely weak full agonists. [ Gly2 -A]-insulin displays 0.05% of the potency of bovine insulin, whereas [Ala2-A]insulin assays at 0.4% of the activity of the natural hormone. We conclude that the presence of the side chain of isoleucine at position A2 is a critical requirement for high biological activity in insulin. The data, together with previous observations, are discussed in connection with an interaction between the side chain of isoleucine-A2 and the phenolic ring system of tyrosine-A19, which are in van der Waals contact in crystalline insulin. This interaction may be required to permit the molecule to assume a conformation consistent with dimerization and with binding to the insulin receptor.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
27
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1405-13
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
1984
pubmed:articleTitle
Critical role of the A2 amino acid residue in the biological activity of insulin: [2-glycine-A]- and [2-alanine-A]insulins.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.