View in EDS

Design and NMR-Based Screening of LEF, a Library of Chemical Fragments with Different Local Environment of Fluorine.

Saved in:
Bibliographic Details
Title: Design and NMR-Based Screening of LEF, a Library of Chemical Fragments with Different Local Environment of Fluorine.
Authors: Vulpetti, Anna1 anna.vulpetti@novartis.com, Hommel, Ulrich1, Landrum, Gregory1, Lewis, Richard1, Dalvit, Claudio1,2 claudio.dalvit@iit.it
Source: Journal of the American Chemical Society. 9/16/2009, Vol. 131 Issue 36, p12949-12959. 11p. 1 Chart, 12 Graphs.
Subjects: Fluorine, Nuclear magnetic resonance, Carrier proteins, Chemical research, Halogens
Abstract: A novel strategy for the design of a fluorinated fragment library that takes into account the local environment of fluorine is described. The procedure, based on a fluorine fingerprints descriptor, and the criteria used in the design, selection, and construction of the library are presented. The library, named LEF (Local Environment of Fluorine), combined with 19F NMR ligand-based screening experiments represents an efficient and sensitive approach for the initial fragment identification within a fragment-based drug discovery project and for probing the presence of fluorophilic protein environments. Proper setup of the method, according to described theoretical simulations, allows the detection of very weak-affinity ligands and the detection of multiple ligands present within the same tested mixture, thus capturing all the potential fragments interacting with the receptor. These NMR hits are then used in the FAXS experiments for the fragment optimization process and for the follow-up screening aimed at identifying other chemical scaffolds relevant for the binding to the receptor. [ABSTRACT FROM AUTHOR]
Copyright of Journal of the American Chemical Society is the property of American Chemical Society and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Engineering Source
FullText Text:
  Availability: 0
Header DbId: egs
DbLabel: Engineering Source
An: 44466047
AccessLevel: 6
PubType: Academic Journal
PubTypeId: academicJournal
PreciseRelevancyScore: 0
IllustrationInfo
Items – Name: Title
  Label: Title
  Group: Ti
  Data: Design and NMR-Based Screening of LEF, a Library of Chemical Fragments with Different Local Environment of Fluorine.
– Name: Author
  Label: Authors
  Group: Au
  Data: <searchLink fieldCode="AR" term="%22Vulpetti%2C+Anna%22">Vulpetti, Anna</searchLink><relatesTo>1</relatesTo><i> anna.vulpetti@novartis.com</i><br /><searchLink fieldCode="AR" term="%22Hommel%2C+Ulrich%22">Hommel, Ulrich</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Landrum%2C+Gregory%22">Landrum, Gregory</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Lewis%2C+Richard%22">Lewis, Richard</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Dalvit%2C+Claudio%22">Dalvit, Claudio</searchLink><relatesTo>1,2</relatesTo><i> claudio.dalvit@iit.it</i>
– Name: TitleSource
  Label: Source
  Group: Src
  Data: <searchLink fieldCode="JN" term="%22Journal+of+the+American+Chemical+Society%22">Journal of the American Chemical Society</searchLink>. 9/16/2009, Vol. 131 Issue 36, p12949-12959. 11p. 1 Chart, 12 Graphs.
– Name: Subject
  Label: Subjects
  Group: Su
  Data: <searchLink fieldCode="DE" term="%22Fluorine%22">Fluorine</searchLink><br /><searchLink fieldCode="DE" term="%22Nuclear+magnetic+resonance%22">Nuclear magnetic resonance</searchLink><br /><searchLink fieldCode="DE" term="%22Carrier+proteins%22">Carrier proteins</searchLink><br /><searchLink fieldCode="DE" term="%22Chemical+research%22">Chemical research</searchLink><br /><searchLink fieldCode="DE" term="%22Halogens%22">Halogens</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: A novel strategy for the design of a fluorinated fragment library that takes into account the local environment of fluorine is described. The procedure, based on a fluorine fingerprints descriptor, and the criteria used in the design, selection, and construction of the library are presented. The library, named LEF (Local Environment of Fluorine), combined with 19F NMR ligand-based screening experiments represents an efficient and sensitive approach for the initial fragment identification within a fragment-based drug discovery project and for probing the presence of fluorophilic protein environments. Proper setup of the method, according to described theoretical simulations, allows the detection of very weak-affinity ligands and the detection of multiple ligands present within the same tested mixture, thus capturing all the potential fragments interacting with the receptor. These NMR hits are then used in the FAXS experiments for the fragment optimization process and for the follow-up screening aimed at identifying other chemical scaffolds relevant for the binding to the receptor. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Journal of the American Chemical Society is the property of American Chemical Society and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=egs&AN=44466047
RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.1021/ja905207t
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        PageCount: 11
        StartPage: 12949
    Subjects:
      – SubjectFull: Fluorine
        Type: general
      – SubjectFull: Nuclear magnetic resonance
        Type: general
      – SubjectFull: Carrier proteins
        Type: general
      – SubjectFull: Chemical research
        Type: general
      – SubjectFull: Halogens
        Type: general
    Titles:
      – TitleFull: Design and NMR-Based Screening of LEF, a Library of Chemical Fragments with Different Local Environment of Fluorine.
        Type: main
  BibRelationships:
    HasContributorRelationships:
      – PersonEntity:
          Name:
            NameFull: Vulpetti, Anna
      – PersonEntity:
          Name:
            NameFull: Hommel, Ulrich
      – PersonEntity:
          Name:
            NameFull: Landrum, Gregory
      – PersonEntity:
          Name:
            NameFull: Lewis, Richard
      – PersonEntity:
          Name:
            NameFull: Dalvit, Claudio
    IsPartOfRelationships:
      – BibEntity:
          Dates:
            – D: 16
              M: 09
              Text: 9/16/2009
              Type: published
              Y: 2009
          Identifiers:
            – Type: issn-print
              Value: 00027863
          Numbering:
            – Type: volume
              Value: 131
            – Type: issue
              Value: 36
          Titles:
            – TitleFull: Journal of the American Chemical Society
              Type: main
ResultId 1