liu.seSearch for publications in DiVA
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • 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
Investigation of alpha-phenylnorstatine and alpha-benzylnorstatine as transition state isostere motifs in the search for new BACE-1 inhibitors
Uppsala University.
Uppsala University.
Uppsala University.
Uppsala University.
Show others and affiliations
2011 (English)In: BIOORGANIC and MEDICINAL CHEMISTRY, ISSN 0968-0896, Vol. 19, no 1, 145-155 p.Article in journal (Refereed) Published
Abstract [en]

Inhibition of the BACE-1 protease enzyme has over the recent decade developed into a promising drug strategy for Alzheimer therapy. In this report, more than 20 new BACE-1 protease inhibitors based on alpha-phenylnorstatine, alpha-benzylnorstatine, iso-serine, and beta-alanine moieties have been prepared. The inhibitors were synthesized by applying Fmoc solid phase methodology and evaluated for their inhibitory properties. The most potent inhibitor, tert-alcohol containing (R)-12 (IC50 = 0.19 mu M) was co-crystallized in the active site of the BACE-1 protease, furnishing a novel binding mode in which the N-terminal amine makes a hydrogen bond to one of the catalytic aspartic acids.

Place, publisher, year, edition, pages
Elsevier Science B.V., Amsterdam. , 2011. Vol. 19, no 1, 145-155 p.
Keyword [en]
Alzheimers disease, BACE-1 inhibitors, tert-Hydroxyl, Transition state mimic, alpha-Phenylnorstatine, alpha-Benzylnorstatine
National Category
Engineering and Technology
Identifiers
URN: urn:nbn:se:liu:diva-65957DOI: 10.1016/j.bmc.2010.11.042ISI: 000285724800014OAI: oai:DiVA.org:liu-65957DiVA: diva2:400662
Available from: 2011-02-28 Created: 2011-02-28 Last updated: 2011-02-28

Open Access in DiVA

No full text

Other links

Publisher's full text

Authority records BETA

Rosenqvist, Åsa

Search in DiVA

By author/editor
Rosenqvist, Åsa
By organisation
Organic Chemistry The Institute of Technology
Engineering and Technology

Search outside of DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 34 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • 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