umu.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Design, synthesis and evaluation of a PLG tripeptidomimetic based on a pyridine scaffold
Umeå University, Faculty of Science and Technology, Department of Chemistry.
Show others and affiliations
2004 (English)In: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 47, no 26, 6595-6602 p.Article in journal (Refereed) Published
Abstract [en]

A 2,3,4-substituted pyridine derivative has been identified as a potential tripeptidomimetic scaffold. The design of the scaffold was based on conformational and electrostatic comparisons with a natural tripeptide. The scaffold has been used in the synthesis of a Pro-Leu-Gly-NH2 (PLG) mimetic. The different substituents in the 2-, 3-, and 4-positions of the pyridine ring were introduced via an aromatic nucleophilic substitution reaction, a "halogen-dancing" reaction, and a Grignard coupling of a Boc-protected amino aldehyde, respectively. The synthetic route involves eight steps and provides the mimetic in 20% overall yield. The pyridine based PLG-mimetic was evaluated for its ability to enhance the maximum response of the dopamine agonist N-propylapomorphine (NPA) at human D2 receptors using a cell based assay (the R-SAT assay). The dose-response curve of the mimetic was found to exhibit a down-turn phase, similar to that of PLG. In addition, the mimetic was more potent than PLG to enhance the NPA response; the maximum response was found to be 146% at 10 nM concentration, as compared to 115% for PLG at the same concentration. Interestingly, conformational analysis by molecular modeling showed that the pyridine mimetic cannot adopt a type II -turn conformation that previously has been suggested to be the bioactive conformation of PLG.

Place, publisher, year, edition, pages
American Chemical Society , 2004. Vol. 47, no 26, 6595-6602 p.
Identifiers
URN: urn:nbn:se:umu:diva-14230DOI: doi:10.1021/jm049484qISI: 000225748500021OAI: oai:DiVA.org:umu-14230DiVA: diva2:153901
Available from: 2007-05-24 Created: 2007-05-24 Last updated: 2011-01-28Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Authority records BETA

Boström, DanKihlberg, Jan

Search in DiVA

By author/editor
Saitton, StinaBoström, DanKihlberg, Jan
By organisation
Department of Chemistry
In the same journal
Journal of Medicinal Chemistry

Search outside of DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 44 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf