Genetically engineered two-warhead evasins provide a method to achieve precision targeting of disease-relevant chemokine subsets.

ABSTRACT: Both CC and CXC-class chemokines drive inflammatory disease. Tick salivary chemokine-binding proteins (CKBPs), or evasins, specifically bind subsets of CC- or CXC-chemokines, and could precisely target disease-relevant chemokines. Here we have used yeast surface display to identify two tick evasins: a CC-CKBP, P1243 from Amblyomma americanum and a CXC-CKBP, P1156 from Ixodes ricinus. P1243 binds 11 CC-chemokines with K_d < 10 nM, and 10 CC-chemokines with K_d between 10 and 100 nM. P1156 binds two ELR + CXC-chemokines with K_d < 10 nM, and four ELR + CXC-chemokines with K_d between 10 and 100 nM. Both CKBPs neutralize chemokine activity with IC₅₀ < 10 nM in cell migration assays. As both CC- and CXC-CKBP activities are desirable in a singl

SUBMITTER: Alenazi Y 

PROVIDER: S-EPMC5910400 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature