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PACAP-Derived Carriers: Mechanisms and Applications

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Book cover Pituitary Adenylate Cyclase Activating Polypeptide — PACAP

Part of the book series: Current Topics in Neurotoxicity ((Current Topics Neurotoxicity,volume 11))

Abstract

One of the main problems in therapeutic efficiency lies in the crossing of physiological barriers and cellular membranes. Therefore, significant efforts have been made to develop agents that cross these barriers and deliver therapeutic agents into intracellular compartments. In recent years, a large amount of data on the use of peptides as delivery agents has accumulated. Among the known cell-penetrating peptides (CPP), sequences derived from the native peptide hormone pituitary adenylate cyclase-activating polypeptide (PACAP) have recently proven to translocate different bioactive molecules across cellular membranes. PACAP, a hypophysiotropic neurohormone, participates in the regulation of multiple functions. The recent discovery of intracellular PACAP receptors in the brain and the testis as well as the physicochemical characteristics of PACAP, i.e., extended α-helix containing basic residues, prompted the evaluation of its cell-penetrating properties in a receptor-independent manner. In this review, we cover the current knowledge concerning the structural requirements, mechanistic assumptions, and metabolic features of these peptides as well as experiments demonstrating their unique carrier potential.

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Abbreviations

BBB:

Blood–brain barrier

BiFC:

Bimolecular fluorescence complementation

cAMP:

Cyclic adenosine monophosphate

CNS:

Central nervous system

CPP:

Cell-penetrating peptides

Disc:

1,3-dihydro-2H-isoindole carboxylic acid

DPC:

Dodecylphosphocholine

DPP IV:

Dipeptidylpeptidase IV

FITC:

Fluorescein isothiocyanate

GAGs:

Glycosaminoglycans

GPCR:

G protein-coupled receptors

hCT:

Human calcitonin

LDH:

Lactate dehydrogenase

MTT:

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

NEP:

Neutral endopeptidase

PAC1:

Pituitary adenylate cyclase-activating polypeptide type 1 receptor

PACAP:

Pituitary adenylate cyclase-activating polypeptide

PACAP27:

27-amino acid isoform of PACAP

PACAP38:

38-amino acid isoform of PACAP

PTS-6:

Peptide transport system-6

VIP:

Vasoactive intestinal peptide

VPAC1:

VIP/PACAP type 1 receptor

VPAC2:

VIP/PACAP type 2 receptor

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Acknowledgements

This work was supported by the Canadian Institutes of Health Research (AF; FRN102734), the Fonds de recherche du Québec-Nature et technologies (DC; 188882), and the Natural Sciences and Engineering Research Council of Canada (SB; 1557119).

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Authors and Affiliations

  1. Groupe de Recherche en Ingénierie des Peptides et en Pharmacothérapie, Institut national de la recherche scientifique, INRS—Institut Armand-Frappier, 531 boul. des Prairies, Laval, QC, Canada, H7V 1B7

    David Chatenet

  2. Laboratoire d’études moléculaires et pharmacologiques des peptides, Institut national de la recherche scientifique, INRS—Institut Armand-Frappier, 531 boul. des Prairies, Laval, QC, Canada, H7V 1B7

    Alain Fournier

  3. Département de Chimie, Université du Québec à Montréal, Montréal, QC, Canada, H3C 3P8

    Steve Bourgault

  4. Quebec Network for Research on Protein Function, Engineering and Applications, PROTEO, Québec, QC, Canada

    Steve Bourgault

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  1. David Chatenet
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  2. Alain Fournier
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  3. Steve Bourgault
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Correspondence to David Chatenet .

Editor information

Editors and Affiliations

  1. Department of Anatomy MTA-PTE “Lendulet” PACAP Research Team, University of Pecs, Pecs, Hungary

    Dora Reglodi

  2. Department of Anatomy MTA-PTE “Lendulet” PACAP Research Team, University of Pecs, Pecs, Hungary

    Andrea Tamas

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Chatenet, D., Fournier, A., Bourgault, S. (2016). PACAP-Derived Carriers: Mechanisms and Applications. In: Reglodi, D., Tamas, A. (eds) Pituitary Adenylate Cyclase Activating Polypeptide — PACAP. Current Topics in Neurotoxicity, vol 11. Springer, Cham. https://doi.org/10.1007/978-3-319-35135-3_9

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