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Development of photo-crosslinking reagents for protein kinase–substrate interactions

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Title: Development of photo-crosslinking reagents for protein kinase–substrate interactions
Authors: Parang, Keykavous, Kohn, Jeffrey A., Saldanha, S. Adrian, Cole, Philip A. pcole@jhmi.edu
Source: FEBS Letters. Jun2002, Vol. 520 Issue 1-3, p156. 5p.
Subjects: Protein kinases, Nucleotides, Protein-tyrosine kinases
Abstract: The identification of relevant protein kinase–protein substrate partners remains a serious challenge on a genome-wide scale. The design and synthesis of a photo-activatable nucleotide reagent to crosslink protein kinases with their substrates is described in which an azido group is appended to the γ-phosphoryl and purine moieties of ATP. In the absence of UV, compounds of this class were shown to act as competitive inhibitors versus ATP and non-competitive inhibitors versus peptide substrate for the protein tyrosine kinase Csk, suggesting that they can form a ternary complex with kinase and protein substrate. In vitro experiments with protein kinases indicate the bifunctional reagent can induce covalent protein–protein crosslinking that is dependent on UV irradiation. That significant kinase–substrate crosslinking occurs is suggested by the fact that this crosslinking is competitively inhibited by ATP. The crosslinked adducts can be readily cleaved by phosphodiesterase which supports the model for crosslinking and provides a simple method to deconvolute the linked protein partners. [Copyright &y& Elsevier]
Copyright of FEBS Letters is the property of Wiley-Blackwell 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
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Header DbId: egs
DbLabel: Engineering Source
An: 7818453
AccessLevel: 6
PubType: Academic Journal
PubTypeId: academicJournal
PreciseRelevancyScore: 0
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  Data: Development of photo-crosslinking reagents for protein kinase–substrate interactions
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  Data: <searchLink fieldCode="AR" term="%22Parang%2C+Keykavous%22">Parang, Keykavous</searchLink><br /><searchLink fieldCode="AR" term="%22Kohn%2C+Jeffrey+A%2E%22">Kohn, Jeffrey A.</searchLink><br /><searchLink fieldCode="AR" term="%22Saldanha%2C+S%2E+Adrian%22">Saldanha, S. Adrian</searchLink><br /><searchLink fieldCode="AR" term="%22Cole%2C+Philip+A%2E%22">Cole, Philip A.</searchLink><i> pcole@jhmi.edu</i>
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  Data: <searchLink fieldCode="JN" term="%22FEBS+Letters%22">FEBS Letters</searchLink>. Jun2002, Vol. 520 Issue 1-3, p156. 5p.
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  Data: <searchLink fieldCode="DE" term="%22Protein+kinases%22">Protein kinases</searchLink><br /><searchLink fieldCode="DE" term="%22Nucleotides%22">Nucleotides</searchLink><br /><searchLink fieldCode="DE" term="%22Protein-tyrosine+kinases%22">Protein-tyrosine kinases</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: The identification of relevant protein kinase–protein substrate partners remains a serious challenge on a genome-wide scale. The design and synthesis of a photo-activatable nucleotide reagent to crosslink protein kinases with their substrates is described in which an azido group is appended to the γ-phosphoryl and purine moieties of ATP. In the absence of UV, compounds of this class were shown to act as competitive inhibitors versus ATP and non-competitive inhibitors versus peptide substrate for the protein tyrosine kinase Csk, suggesting that they can form a ternary complex with kinase and protein substrate. In vitro experiments with protein kinases indicate the bifunctional reagent can induce covalent protein–protein crosslinking that is dependent on UV irradiation. That significant kinase–substrate crosslinking occurs is suggested by the fact that this crosslinking is competitively inhibited by ATP. The crosslinked adducts can be readily cleaved by phosphodiesterase which supports the model for crosslinking and provides a simple method to deconvolute the linked protein partners. [Copyright &y& Elsevier]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of FEBS Letters is the property of Wiley-Blackwell 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.)
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RecordInfo BibRecord:
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      – Type: doi
        Value: 10.1016/S0014-5793(02)02778-3
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      – Code: eng
        Text: English
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        PageCount: 5
        StartPage: 156
    Subjects:
      – SubjectFull: Protein kinases
        Type: general
      – SubjectFull: Nucleotides
        Type: general
      – SubjectFull: Protein-tyrosine kinases
        Type: general
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      – TitleFull: Development of photo-crosslinking reagents for protein kinase–substrate interactions
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            NameFull: Parang, Keykavous
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            NameFull: Kohn, Jeffrey A.
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            NameFull: Saldanha, S. Adrian
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            NameFull: Cole, Philip A.
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              Text: Jun2002
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              Y: 2002
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              Value: 520
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