Probing Functional Heteromeric Chemokine Protein–Protein Interactions through Conformation‐Assisted Oxime Ligation
Abstract: Protein–protein interactions (PPIs) govern most processes in living cells. Current drug development strategies are aimed at disrupting or stabilizing PPIs, which require a thorough understanding of PPI mechanisms. Examples of such PPIs are heteromeric chemokine interactions that are potentially involved in pathological disorders such as cancer, atherosclerosis, and HIV. It remains unclear whether this functional modulation is mediated by heterodimer formation or by the additive effects of mixed chemokines on their respective receptors. To address this issue, we report the synthesis of a covalent RANTES‐PF4 heterodimer (termed OPRAH) by total chemical synthesis and oxime ligation, with an acceleration of the final ligation step driven by PPIs between RANTES and PF4. Compared to mixed separate chemokines, OPRAH exhibited increased biological activity, thus providing evidence that physical formation of the heterodimer indeed mediates enhanced function.
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Erschienen in
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Probing Functional Heteromeric Chemokine Protein–Protein Interactions through Conformation‐Assisted Oxime Ligation ; volume:55 ; number:48 ; year:2016 ; pages:14963-14966 ; extent:4
Angewandte Chemie / International edition. International edition ; 55, Heft 48 (2016), 14963-14966 (gesamt 4)
- Urheber
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Agten, Stijn M.
Koenen, Rory R.
Ippel, Hans
Eckardt, Veit
von Hundelshausen, Philipp
Mayo, Kevin H.
Weber, Christian
Hackeng, Tilman M.
- DOI
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10.1002/anie.201607036
- URN
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urn:nbn:de:101:1-2022103007504180085094
- Rechteinformation
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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15.08.2025, 07:38 MESZ
Datenpartner
Deutsche Nationalbibliothek. Bei Fragen zum Objekt wenden Sie sich bitte an den Datenpartner.
Beteiligte
- Agten, Stijn M.
- Koenen, Rory R.
- Ippel, Hans
- Eckardt, Veit
- von Hundelshausen, Philipp
- Mayo, Kevin H.
- Weber, Christian
- Hackeng, Tilman M.
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