Rational Design of Chemokine SDF-1 Analogs with Agonist Activity for the CXCR4 Receptor and the Capacity to Rapidly Mobilize PMN and Hematopoietic Progenitor Cells in Mice

Author(s): Ahmed Merzouk, Donald Wong, Hassan Salari, Huimin Bian, Seiji Fukuda, Louis M. Pelus.

Journal Name: Letters in Drug Design & Discovery

Volume 1 , Issue 2 , 2004

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We designed SDF-1α / CXCL12 (1) analogs to improve in vivo bioactivity. A linear analogue (2) consisting of AA1-14 of (1) joined by (Gly)4 to AA56-67 binds CXCR4, but with ∼100-fold less affinity. Cyclized analogs (3) and (4) were 2-3-fold more active. Substitution of the cysteines in analog (3) forming analog (5) prevented dimerization and increased plasma stability. Analogs (3) and (5) rapidly mobilized neutrophils and hematopoietic progenitor cells and synergized with G-CSF in normal mice.

Keywords: agonist peptides, stem cell mobilization, hematopoiesis, cxcr4, rational design

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Article Details

Year: 2004
Page: [126 - 134]
Pages: 9
DOI: 10.2174/1570180043485608
Price: $58

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