Skip to main content
Journal cover image

Profiling heparin-chemokine interactions using synthetic tools.

Publication ,  Journal Article
de Paz, JL; Moseman, EA; Noti, C; Polito, L; von Andrian, UH; Seeberger, PH
Published in: ACS Chem Biol
November 20, 2007

Glycosaminoglycans (GAGs), such as heparin or heparan sulfate, are required for the in vivo function of chemokines. Chemokines play a crucial role in the recruitment of leukocyte subsets to sites of inflammation and lymphocytes trafficking. GAG-chemokine interactions mediate cell migration and determine which leukocyte subsets enter tissues. Identifying the exact GAC sequences that bind to particular chemokines is key to understand chemokine function at the molecular level and develop strategies to interfere with chemokine-mediated processes. Here, we characterize the heparin binding profiles of eight chemokines (CCL21, IL-8, CXCL12, CXCL13, CCL19, CCL25, CCL28, and CXCL16) by employing heparin microarrays containing a small library of synthetic heparin oligosaccharides. The chemokines differ significantly in their interactions with heparin oligosaccharides: While some chemokines, (e.g., CCL21) strongly bind to a hexasaccharide containing the GlcNSO3(6-OSO3)-IdoA(2-OSO3) repeating unit, CCL19 does not bind and CXCL12 binds only weakly. The carbohydrate microarray binding results were validated by surface plasmon resonance experiments. In vitro chemotaxis assays revealed that dendrimers coated with the fully sulfated heparin hexasaccharide inhibit lymphocyte migration toward CCL21. Migration toward CXCL12 or CCL19 was not affected. These in vitro homing assays indicate that multivalent synthetic heparin dendrimers inhibit the migration of lymphocytes toward certain chemokine gradients by blocking the formation of a chemokine concentration gradient on GAG endothelial chains. These findings are in agreement with preliminary in vivo measurements of circulating lymphocytes. The results presented here contribute to the understanding of GAG-chemokine interactions, a first step toward the design of novel drugs that modulate chemokine activity.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

ACS Chem Biol

DOI

EISSN

1554-8937

Publication Date

November 20, 2007

Volume

2

Issue

11

Start / End Page

735 / 744

Location

United States

Related Subject Headings

  • Protein Binding
  • Protein Array Analysis
  • Organic Chemistry
  • Heparin
  • Drug Evaluation, Preclinical
  • Drug Design
  • Chemokines
  • 34 Chemical sciences
  • 31 Biological sciences
  • 06 Biological Sciences
 

Citation

APA
Chicago
ICMJE
MLA
NLM
de Paz, J. L., Moseman, E. A., Noti, C., Polito, L., von Andrian, U. H., & Seeberger, P. H. (2007). Profiling heparin-chemokine interactions using synthetic tools. ACS Chem Biol, 2(11), 735–744. https://doi.org/10.1021/cb700159m
Paz, Jose L. de, E Ashley Moseman, Christian Noti, Laura Polito, Ulrich H. von Andrian, and Peter H. Seeberger. “Profiling heparin-chemokine interactions using synthetic tools.ACS Chem Biol 2, no. 11 (November 20, 2007): 735–44. https://doi.org/10.1021/cb700159m.
de Paz JL, Moseman EA, Noti C, Polito L, von Andrian UH, Seeberger PH. Profiling heparin-chemokine interactions using synthetic tools. ACS Chem Biol. 2007 Nov 20;2(11):735–44.
de Paz, Jose L., et al. “Profiling heparin-chemokine interactions using synthetic tools.ACS Chem Biol, vol. 2, no. 11, Nov. 2007, pp. 735–44. Pubmed, doi:10.1021/cb700159m.
de Paz JL, Moseman EA, Noti C, Polito L, von Andrian UH, Seeberger PH. Profiling heparin-chemokine interactions using synthetic tools. ACS Chem Biol. 2007 Nov 20;2(11):735–744.
Journal cover image

Published In

ACS Chem Biol

DOI

EISSN

1554-8937

Publication Date

November 20, 2007

Volume

2

Issue

11

Start / End Page

735 / 744

Location

United States

Related Subject Headings

  • Protein Binding
  • Protein Array Analysis
  • Organic Chemistry
  • Heparin
  • Drug Evaluation, Preclinical
  • Drug Design
  • Chemokines
  • 34 Chemical sciences
  • 31 Biological sciences
  • 06 Biological Sciences