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A MIF-Derived Cyclopeptide that Inhibits MIF Binding and Atherogenic Signaling via the Chemokine Receptor CXCR2.
Krammer, Christine; Kontos, Christos; Dewor, Manfred; Hille, Kathleen; Dalla Volta, Beatrice; El Bounkari, Omar; Tas, Karin; Sinitski, Dzmitry; Brandhofer, Markus; Megens, Remco T A; Weber, Christian; Schultz, Joshua R; Bernhagen, Jürgen; Kapurniotu, Aphrodite.
Afiliação
  • Krammer C; Division of Vascular Biology, Institute for Stroke and Dementia Research (ISD), LMU Klinikum, Ludwig-Maximilians-Universität (LMU), Feodor-Lynen-Straße 17, 81377, Munich, Germany.
  • Kontos C; Division of Peptide Biochemistry, TUM School of Life Sciences, Technische Universität München (TUM), Emil-Erlenmeyer-Forum 5, 85354, Freising, Germany.
  • Dewor M; Institute of Biochemistry and Molecular Cell Biology, University Hospital, RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany.
  • Hille K; Division of Peptide Biochemistry, TUM School of Life Sciences, Technische Universität München (TUM), Emil-Erlenmeyer-Forum 5, 85354, Freising, Germany.
  • Dalla Volta B; Division of Peptide Biochemistry, TUM School of Life Sciences, Technische Universität München (TUM), Emil-Erlenmeyer-Forum 5, 85354, Freising, Germany.
  • El Bounkari O; Division of Vascular Biology, Institute for Stroke and Dementia Research (ISD), LMU Klinikum, Ludwig-Maximilians-Universität (LMU), Feodor-Lynen-Straße 17, 81377, Munich, Germany.
  • Tas K; Institute of Biochemistry and Molecular Cell Biology, University Hospital, RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany.
  • Sinitski D; Division of Peptide Biochemistry, TUM School of Life Sciences, Technische Universität München (TUM), Emil-Erlenmeyer-Forum 5, 85354, Freising, Germany.
  • Brandhofer M; Division of Vascular Biology, Institute for Stroke and Dementia Research (ISD), LMU Klinikum, Ludwig-Maximilians-Universität (LMU), Feodor-Lynen-Straße 17, 81377, Munich, Germany.
  • Megens RTA; Division of Vascular Biology, Institute for Stroke and Dementia Research (ISD), LMU Klinikum, Ludwig-Maximilians-Universität (LMU), Feodor-Lynen-Straße 17, 81377, Munich, Germany.
  • Weber C; Institute for Cardiovascular Prevention, LMU Klinikum, Ludwig-Maximilians-Universität (LMU), Pettenkoferstrasse 8a and 9, 80336, Munich, Germany.
  • Schultz JR; Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Universiteitssingel 50, 6229, Maastricht (The, Netherlands.
  • Bernhagen J; Institute for Cardiovascular Prevention, LMU Klinikum, Ludwig-Maximilians-Universität (LMU), Pettenkoferstrasse 8a and 9, 80336, Munich, Germany.
  • Kapurniotu A; Munich Cluster for Systems Neurology (SyNergy), Feodor-Lynen-Straße 17, 81377, Munich, Germany.
Chembiochem ; 22(6): 1012-1019, 2021 03 16.
Article em En | MEDLINE | ID: mdl-33125165
ABSTRACT
Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine and atypical chemokine with a key role in inflammatory diseases including atherosclerosis. Key atherogenic functions of MIF are mediated by noncognate interaction with the chemokine receptor CXCR2. The MIF N-like loop comprising the sequence 47-56 is an important structural determinant of the MIF/CXCR2 interface and MIF(47-56) blocks atherogenic MIF activities. However, the mechanism and critical structure-activity information within this sequence have remained elusive. Here, we show that MIF(47-56) directly binds to CXCR2 to compete with MIF receptor activation. By using alanine scanning, essential and dispensable residues were identified. Moreover, MIF(cyclo10), a designed cyclized variant of MIF(47-56), inhibited key inflammatory and atherogenic MIF activities in vitro and in vivo/ex vivo, and exhibited strongly improved resistance to proteolytic degradation in human plasma in vitro, thus suggesting that it could serve as a promising basis for MIF-derived anti-atherosclerotic peptides.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Peptídeos Cíclicos / Fatores Inibidores da Migração de Macrófagos / Receptores de Interleucina-8B Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Peptídeos Cíclicos / Fatores Inibidores da Migração de Macrófagos / Receptores de Interleucina-8B Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article