Engineering and screening the N-terminus of chemokines for drug discovery

Andy Chevigné*, Virginie Fievez, Jean Claude Schmit, Sabrina Deroo

*Corresponding author for this work

    Research output: Contribution to journalArticleResearchpeer-review

    22 Citations (Scopus)


    Chemokines are small chemoattractive proteins involved in many important physiological and pathological processes such as leukocyte mobilisation, inflammation, cancer and HIV-1 infection. The N-terminus of chemokines was shown to be crucial for interaction and activation with their cognate receptors. Therefore, multiple strategies including elongation, truncation, mutagenesis or chemical modifications of chemokine N-terminus were developed to identify analogues with modified selectivity displaying antagonist or enhanced agonist activities. Library approaches allowed fast screening of a large number of such chemokine variants and led to the identification of promising therapeutic candidates. Additional studies were able to reduce the chemokine to the size of a peptide while retaining its receptor affinity and selectivity. In analogy to full length chemokines, peptides derived from the chemokine N-terminal sequence were improved by mutagenesis, elongation and truncation approaches to develop potential therapeutic molecules used in various clinical trials. Altogether these studies demonstrated the pharmacophore potential of the chemokine N-terminus and its vast modulation properties to develop analogues with great therapeutic value for a large set of pathologies.

    Original languageEnglish
    Pages (from-to)1438-1456
    Number of pages19
    JournalBiochemical Pharmacology
    Issue number10
    Publication statusPublished - 15 Nov 2011


    • Antagonists
    • CCR5
    • CXCR4
    • Chemokine analogues
    • Chemokine receptors
    • Therapeutic peptides


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