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@ARTICLE{Pissarek:276645,
author = {Pissarek, Margit},
title = {{P}otential {PET} {L}igands for {I}maging of {C}erebral
{VPAC} and {PAC} {R}eceptors: {A}re {N}on-{P}eptide {S}mall
{M}olecules {S}uperior to {P}eptide {C}ompounds?},
journal = {World Journal of Neuroscience},
volume = {05},
number = {05},
issn = {2162-2019},
address = {Irvine, CA},
publisher = {Scientific Research Publ.},
reportid = {FZJ-2015-06973},
pages = {364 - 384},
year = {2015},
abstract = {Pituitary adenylate cyclase activating polypeptide (PACAP)
and vasoactive intestinal peptide (VIP) have been known for
decades to mediate neuroendocrine and vasodilative actions
via G-protein-coupled receptors of Class B. These are
targets of imaging probes for positron emission tomography
(PET) or single photon emission tomography (SPECT) in tumor
diagnostics and tumor grading. However, they play only a
subordinate role in the development of tracers for brain
imaging. Difficulties in development of non-peptide ligands
typical for cerebral receptors of PACAP and VIP are shared
by all members of Class B receptor family. Essential
landmarks have been confirmed for understanding of
structural details of Class B receptor molecular signalling
during the last five years. High relevance in the
explanation of problems in ligand development for these
receptors is admitted to the large N-terminal ectodomain
markedly different from Class A receptor binding sites and
poorly suitable as orthosteric binding sites for the most
small-molecule compounds. The present study is focused on
the recently available receptor ligands for PAC1, VPAC1 and
VPAC2 receptors as well as potential small-molecule lead
structures suitable for use in PET or SPECT. Recently,
biaryl, cyanothiophene and pentanamide structures with
affinities in nM-range have been proposed as non-peptide
ligands at VPAC1 and VPAC2 receptors. However, most of these
ligands have been classified as non-competitive related to
the orthosteric binding site of endogenous peptide ligands
of VPAC receptors. For PAC1 receptors have been identified
hydrazide compounds for which an inhibitory and potentially
competitive mechanism of receptor binding has been
postulated based on molecular docking studies.},
cin = {INM-5},
ddc = {610},
cid = {I:(DE-Juel1)INM-5-20090406},
pnm = {315 - Imaging and radiooncology (POF3-315)},
pid = {G:(DE-HGF)POF3-315},
typ = {PUB:(DE-HGF)16},
doi = {10.4236/wjns.2015.55036},
url = {https://juser.fz-juelich.de/record/276645},
}