Application of ring-closing metathesis to Grb2 SH3 domain-binding peptides
Molecular processes depending on protein-protein interactions can use consensus recognition sequences that possess defined secondary structures. Left-handed polyproline II (PPII) helices are a class of secondary structure commonly involved with cellular signal transduction. However, unlike α-helices...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2011
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| _version_ | 1797056687171960832 |
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| author | Liu, F Giubellino, A Simister, P Qian, W Giano, M Feller, S Bottaro, D Burke, T |
| author_facet | Liu, F Giubellino, A Simister, P Qian, W Giano, M Feller, S Bottaro, D Burke, T |
| author_sort | Liu, F |
| collection | OXFORD |
| description | Molecular processes depending on protein-protein interactions can use consensus recognition sequences that possess defined secondary structures. Left-handed polyproline II (PPII) helices are a class of secondary structure commonly involved with cellular signal transduction. However, unlike α-helices, for which a substantial body of work exists regarding applications of ring-closing metathesis (RCM), there are few reports on the stabilization of PPII helices by RCM methodologies. The current study examined the effects of RCM macrocyclization on left-handed PPII helices involved with the SH3 domain-mediated binding of Sos1-Grb2. Starting with the Sos1-derived peptide ''Ac-V1-P2-P3- P4-V 5-P6-P7-R8-R9-R 10-amide,'' RCM macrocyclizations were conducted using alkenyl chains of varying lengths originating from the pyrrolidine rings of the Pro4 and Pro7 residues. The resulting macrocyclic peptides showed increased helicity as indicated by circular dichroism and enhanced abilities to block Grb2-Sos1 interactions in cell lysate pull-down assays. The synthetic approach may be useful in RCM macrocyclizations, where maintenance of proline integrity at both ring junctures is desired. © 2011 Wiley Periodicals, Inc. |
| first_indexed | 2024-03-06T19:26:07Z |
| format | Journal article |
| id | oxford-uuid:1bc47e99-b04a-4e09-9acd-091b716e9a12 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:26:07Z |
| publishDate | 2011 |
| record_format | dspace |
| spelling | oxford-uuid:1bc47e99-b04a-4e09-9acd-091b716e9a122022-03-26T11:02:15ZApplication of ring-closing metathesis to Grb2 SH3 domain-binding peptidesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:1bc47e99-b04a-4e09-9acd-091b716e9a12EnglishSymplectic Elements at Oxford2011Liu, FGiubellino, ASimister, PQian, WGiano, MFeller, SBottaro, DBurke, TMolecular processes depending on protein-protein interactions can use consensus recognition sequences that possess defined secondary structures. Left-handed polyproline II (PPII) helices are a class of secondary structure commonly involved with cellular signal transduction. However, unlike α-helices, for which a substantial body of work exists regarding applications of ring-closing metathesis (RCM), there are few reports on the stabilization of PPII helices by RCM methodologies. The current study examined the effects of RCM macrocyclization on left-handed PPII helices involved with the SH3 domain-mediated binding of Sos1-Grb2. Starting with the Sos1-derived peptide ''Ac-V1-P2-P3- P4-V 5-P6-P7-R8-R9-R 10-amide,'' RCM macrocyclizations were conducted using alkenyl chains of varying lengths originating from the pyrrolidine rings of the Pro4 and Pro7 residues. The resulting macrocyclic peptides showed increased helicity as indicated by circular dichroism and enhanced abilities to block Grb2-Sos1 interactions in cell lysate pull-down assays. The synthetic approach may be useful in RCM macrocyclizations, where maintenance of proline integrity at both ring junctures is desired. © 2011 Wiley Periodicals, Inc. |
| spellingShingle | Liu, F Giubellino, A Simister, P Qian, W Giano, M Feller, S Bottaro, D Burke, T Application of ring-closing metathesis to Grb2 SH3 domain-binding peptides |
| title | Application of ring-closing metathesis to Grb2 SH3 domain-binding peptides |
| title_full | Application of ring-closing metathesis to Grb2 SH3 domain-binding peptides |
| title_fullStr | Application of ring-closing metathesis to Grb2 SH3 domain-binding peptides |
| title_full_unstemmed | Application of ring-closing metathesis to Grb2 SH3 domain-binding peptides |
| title_short | Application of ring-closing metathesis to Grb2 SH3 domain-binding peptides |
| title_sort | application of ring closing metathesis to grb2 sh3 domain binding peptides |
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