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

Ahmed      Merzouk; Donald      Wong; Hassan      Salari; Huimin      Bian; Seiji      Fukuda; Louis   M.   Pelus

Abstract

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

« Previous Next »

Rights & Permissions Print Cite

Letters in Drug Design & Discovery

Title: 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

Volume: 1 Issue: 2

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

Affiliation:

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

Abstract: 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.

Export Options

Export File:

RIS (for EndNote, Reference Manager, ProCite)

BibTeX

Text

Content:

Citation Only

Citation and Abstract

About this article

Cite this article as:

Merzouk Ahmed, Wong Donald, Salari Hassan, Bian Huimin, Fukuda Seiji and Pelus M. Louis, 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, Letters in Drug Design & Discovery 2004; 1 (2) . https://dx.doi.org/10.2174/1570180043485608