Epitope‐Targeted Macrocyclic Peptide Ligand with Picomolar Cooperative Binding to Interleukin‐17F

Epitope‐Targeted Macrocyclic Peptide Ligand with Picomolar Cooperative Binding to... The IL‐17 cytokine family is associated with multiple immune and autoimmune diseases and comprises important diagnostic and therapeutic targets. This work reports the development of epitope‐targeted ligands designed for differential detection of human IL‐17F and its closest homologue IL‐17A. Non‐overlapping and unique epitopes on IL‐17F and IL‐17A were identified by comparative sequence analysis of the two proteins. Synthetic variants of these epitopes were utilized as targets for in situ click screens against a comprehensive library of synthetic peptide macrocycles with 5‐mer variable regions. Single generation screens yielded selective binders for IL‐17F and IL‐17A with low cross‐reactivity. Macrocyclic peptide binders against two distinct IL‐17F epitopes were coupled using variable length chemical linkers to explore the physical chemistry of cooperative binding. The optimized linker length yielded a picomolar affinity binder, while retaining high selectivity. The presented method provides a rational approach towards targeting discontinuous epitopes, similar to what is naturally achieved by many B cell receptors. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Chemistry - A European Journal Wiley

Epitope‐Targeted Macrocyclic Peptide Ligand with Picomolar Cooperative Binding to Interleukin‐17F

Loading next page...
 
/lp/wiley/epitope-targeted-macrocyclic-peptide-ligand-with-picomolar-cooperative-sYCD0Ic6NT
Publisher
Wiley
Copyright
© 2018 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim
ISSN
0947-6539
eISSN
1521-3765
D.O.I.
10.1002/chem.201704752
Publisher site
See Article on Publisher Site

Abstract

The IL‐17 cytokine family is associated with multiple immune and autoimmune diseases and comprises important diagnostic and therapeutic targets. This work reports the development of epitope‐targeted ligands designed for differential detection of human IL‐17F and its closest homologue IL‐17A. Non‐overlapping and unique epitopes on IL‐17F and IL‐17A were identified by comparative sequence analysis of the two proteins. Synthetic variants of these epitopes were utilized as targets for in situ click screens against a comprehensive library of synthetic peptide macrocycles with 5‐mer variable regions. Single generation screens yielded selective binders for IL‐17F and IL‐17A with low cross‐reactivity. Macrocyclic peptide binders against two distinct IL‐17F epitopes were coupled using variable length chemical linkers to explore the physical chemistry of cooperative binding. The optimized linker length yielded a picomolar affinity binder, while retaining high selectivity. The presented method provides a rational approach towards targeting discontinuous epitopes, similar to what is naturally achieved by many B cell receptors.

Journal

Chemistry - A European JournalWiley

Published: Jan 12, 2018

Keywords: ; ; ; ;

References

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create lists to
organize your research

Export lists, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off