Journal article
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 Kd < 10 nM, and 10 CC-chemokines with Kd between 10 and 100 nM. P1156 binds two ELR + CXC-chemokines with Kd < 10 nM, and four ELR + CXC-chemokines with Kd 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 single agent, we have engineered "two-warhead" CKBPs to create single agents that bind and neutralize subsets of CC and CXC chemokines. These results show that tick evasins can be linked to create non-natural proteins that target subsets of CC and CXC chemokines. We suggest that "two-warhead" evasins, designed by matching the activities of parental evasins to CC and CXC chemokines expressed in disease, would achieve precision targeting of inflammatory disease-relevant chemokines by a single agent.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
Actions
Access Document
- Files:
-
-
(Preview, Version of record, pdf, 3.4MB, Terms of use)
-
- Publisher copy:
- 10.1038/s41598-018-24568-9
Authors
- Publisher:
- Nature Publishing Group
- Journal:
- Scientific Reports More from this journal
- Volume:
- 8
- Issue:
- 1
- Pages:
- 6333
- Publication date:
- 2018-04-20
- Acceptance date:
- 2018-04-06
- DOI:
- EISSN:
-
2045-2322
- Pmid:
-
29679010
- Language:
-
English
- Keywords:
- Pubs id:
-
pubs:844998
- UUID:
-
uuid:edaea4ce-ea3d-4b31-a2c0-69d0845d0d33
- Local pid:
-
pubs:844998
- Source identifiers:
-
844998
- Deposit date:
-
2018-05-14
Terms of use
- Copyright holder:
- Bhattacharya et al
- Copyright date:
- 2018
- Notes:
- © The Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
- Licence:
- CC Attribution (CC BY)
If you are the owner of this record, you can report an update to it here: Report update to this record