Screening and characterization of cyclic pentapeptide CXCR4 antagonists/inverse agonists using a pheromone responsive reporter gene in Saccharomyces cerevisiae: Utility of G protein coupled receptor constitutively active mutants

  • Zi-xuan Wang
  • Hirokazu Tamamura
  • Nicole Frilot
  • James Broach
  • Nobutaka Fujii
  • Stephen C. Peiper
Part of the Progress in Inflammation Research book series (PIR)


CXCR4 is a chemokine receptor that belongs to the GPCR superfamily. It specifically transduces the signal of one CXC chemokine ligand, stromal cell derived factor 1 [1, 2], which has been designated CXCL12 in the current nomenclature assigned to members of the chemoattractant cytokine gene family [3]. This GPCR-ligand pair plays a critical role in programming the directed migration of multiple cell types during embryologic development, including neural, endothelial, and hematopoietic progenitors, as well as primordial germ cells [4]. Mice rendered nullizygous for either CXCR4 or CXCL12 by gene targeting die in utero with incomplete formation of the cerebellum, vascular system and the medullary hematopoietic compartment [5]–[7]. During adult life, CXCL12 is a chemoattractant for multiple subsets of leukocyte and exposure to CXCR4 antagonists results in mobilization of (hematopoietic) stem cells [8]. Rare individuals carrying a mutation that results in loss of the normal cytoplasmic tail, either by truncation or translational frame shift, which precludes desensitization following activation have a dominant syndrome characterized by warts, hypogammaglobulinemia, infections, and myelokathexis (retention of myeloid cells in the bone marrow) [9].


Primordial Germ Cell Inverse Agonist Galactosidase Activity CXCR4 Antagonist Biologic Potency 
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Copyright information

© Birkhäuser Verlag Basel/Switzerland 2007

Authors and Affiliations

  • Zi-xuan Wang
    • 1
  • Hirokazu Tamamura
    • 2
  • Nicole Frilot
    • 1
  • James Broach
    • 3
  • Nobutaka Fujii
    • 2
  • Stephen C. Peiper
    • 1
  1. 1.Immunotherapy Center and Department of PathologyMedical College of GeorgiaAugustaUSA
  2. 2.Kyoto UniversityKyotoJapan
  3. 3.Princeton UniversityPrincetonUSA

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