SwePub
Sök i LIBRIS databas

  Extended search

onr:"swepub:oai:DiVA.org:uu-140680"
 

Search: onr:"swepub:oai:DiVA.org:uu-140680" > Identification of a...

  • 1 of 1
  • Previous record
  • Next record
  •    To hitlist
  • Geitmann, Matthis (author)

Identification of a Novel Scaffold for Allosteric Inhibition of Wild Type and Drug Resistant HIV-1 Reverse Transcriptase by Fragment Library Screening

  • Article/chapterEnglish2011

Publisher, publication year, extent ...

  • 2011-01-05
  • American Chemical Society (ACS),2011
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-140680
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-140680URI
  • https://doi.org/10.1021/jm1010513DOI

Supplementary language notes

  • Language:English
  • Summary in:English &language:-1_t

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • A novel scaffold inhibiting wild type and drug resistant variants of human immunodeficiency virus type 1 reverse transcriptase (HIV-1RT) has been identified in a library consisting of 1040 fragments. The fragments were significantly different from already known non-nucleoside reverse transcriptase inhibitors (NNRTIs), as indicated by a Tversky similarity analysis. A screening strategy involving SPR biosensor-based interaction analysis and enzyme inhibition was used. Primary biosensor-based screening, using short concentration series, was followed by analysis of nevirapine competition and enzyme inhibition, thus identifying inhibitory fragments binding to the non-nucleoside reverse transcriptase inhibitor (NNRTI) binding site. Ten hits were discovered, and their affinities and resistance profiles were evaluated with wild type and three drug resistant enzyme variants (K103N, Y181C, and L100I). One fragment exhibited submillimolar K(D) and IC(50) values against all four tested enzyme variants. A substructure comparison between the fragment and 826 structurally diverse published NNRTIs confirmed that the scaffold was novel. The fragment is a bromoindanone with a ligand efficiency of 0.42 kcal/mol(-1).

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Elinder, MalinUppsala universitet,Institutionen för biokemi och organisk kemi(Swepub:uu)maeli424 (author)
  • Seeger, ChristianUppsala universitet,Institutionen för biokemi och organisk kemi(Swepub:uu)chrse403 (author)
  • Brandt, Peter (author)
  • de Esch, Iwan J P (author)
  • Danielson, U Helena,1959-Uppsala universitet,Biokemi,U Helena Danielson(Swepub:uu)helenads (author)
  • Uppsala universitetInstitutionen för biokemi och organisk kemi (creator_code:org_t)

Related titles

  • In:Journal of Medicinal Chemistry: American Chemical Society (ACS)54:3, s. 699-7080022-26231520-4804

Internet link

Find in a library

To the university's database

  • 1 of 1
  • Previous record
  • Next record
  •    To hitlist

Search outside SwePub

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Close

Copy and save the link in order to return to this view