Selective Targeting of Integrin αvβ8 by a Highly Active Cyclic Peptide

Integrins play important roles in
physiological and pathophysiological
processes. Among the RGD-recognizing integrin
subtypes, the αvβ8 receptor is emerging as an attractive
target because of its involvement in various illnesses, such as autoimmune
diseases, viral infections, and cancer. However, its functions have,
so far, not been investigated in living subjects mainly because of
the lack of a selective αvβ8 ligand. Here, we report the
design and potential medical applications of a cyclic octapeptide
as the first highly selective small-molecule ligand for αvβ8.
Remarkably, this compound displays low nanomolar αvβ8
binding affinity and a strong discriminating power of at least 2 orders
of magnitude versus other RGD-recognizing integrins. Peptide functionalization
with fluorescent or radioactive labels enables the selective imaging
of αvβ8-positive cells and tissues. This new probe will
pave the way for detailed characterization of the distinct (patho)­physiological
role of this relatively unexplored integrin, providing a basis to
fully exploit the potential of αvβ8 as a target for molecular
diagnostics and personalized therapy regimens.