Antinociceptive Effects of VV-Hemorphin-5 Peptide Analogues Containing Amino phosphonate Moiety in Mouse Formalin Model of Pain.
Hemorphin analogues
analgesic drugs
formalin test
inflammatory pain
opioid peptides
mice
Journal
Protein and peptide letters
ISSN: 1875-5305
Titre abrégé: Protein Pept Lett
Pays: Netherlands
ID NLM: 9441434
Informations de publication
Date de publication:
2021
2021
Historique:
received:
29
01
2020
revised:
19
06
2020
accepted:
21
06
2020
pubmed:
18
8
2020
medline:
12
6
2021
entrez:
18
8
2020
Statut:
ppublish
Résumé
Hemorphins are endogenous hemoglobin-derived peptides that belong to the family of "atypical" opioid peptides with both affinities to opioid receptors and ability to release other endogenous opioid peptides. In the present study, peptide analogues of Valorphin (VV-hemorphin-5) containing amino phosphonate moiety synthesized by solid-phase peptide synthesis (Fmoc-strategy) were investigated for their potential antinociceptive activities and compared to the reference VV-H in formalin- induced model of acute and inflammatory pain in mice. The hemorphin analogues were prepared by replacement of the one and/or two N-terminal Val in VV-hemorphin5 (VV-H) with ((dimethoxy phosphoryl) methyl)-L-valine and ((dimethoxy phosphoryl) methyl)-L-leucine to obtain the compounds pVV-H, pL-H, and pLV-H. Aiming to additionally prove the importance of amino acid valine, we introduced the ((dimethoxy phosphoryl) methyl)-L-leucine to the N-side of VV-hemorphin-5 (pLVV-H). The experiments were carried out on adult male ICR mice. All peptides were administered intracerebroventricularly at three doses (50, 25 and 12,5 μg/mouse). We have studied the effects of the peptides on acute (1st phase) and inflammatory (2nd phase) pain reaction using un experimental model with intraplantar formalin injection. VV-H showed a significant antinociceptive effect both in the acute and inflammatory phases of the test. Although Valorphin hexa-, hepta-, and octapeptide analogs demonstrated a significant antinociceptive effect, they showed substantial differences considering their effective dose and the phase of the test as compared to the Valorphin. Data showed that modified heptapeptides pVV-H and pLV-H exerted the same or better antinociception in acute and inflammatory pain, in comparison to the reference peptide, while pL-H and pLVV-H analogues were less effective. Our study contributes to the elucidation of the role of Valine and the number of amino acid residues in the structure of hemorphin peptide analogs in their effectiveness in suppressing both acute and inflammatory experimental pain.
Sections du résumé
BACKGROUND
Hemorphins are endogenous hemoglobin-derived peptides that belong to the family of "atypical" opioid peptides with both affinities to opioid receptors and ability to release other endogenous opioid peptides.
OBJECTIVE
In the present study, peptide analogues of Valorphin (VV-hemorphin-5) containing amino phosphonate moiety synthesized by solid-phase peptide synthesis (Fmoc-strategy) were investigated for their potential antinociceptive activities and compared to the reference VV-H in formalin- induced model of acute and inflammatory pain in mice.
METHODS
The hemorphin analogues were prepared by replacement of the one and/or two N-terminal Val in VV-hemorphin5 (VV-H) with ((dimethoxy phosphoryl) methyl)-L-valine and ((dimethoxy phosphoryl) methyl)-L-leucine to obtain the compounds pVV-H, pL-H, and pLV-H. Aiming to additionally prove the importance of amino acid valine, we introduced the ((dimethoxy phosphoryl) methyl)-L-leucine to the N-side of VV-hemorphin-5 (pLVV-H). The experiments were carried out on adult male ICR mice. All peptides were administered intracerebroventricularly at three doses (50, 25 and 12,5 μg/mouse). We have studied the effects of the peptides on acute (1st phase) and inflammatory (2nd phase) pain reaction using un experimental model with intraplantar formalin injection.
RESULTS
VV-H showed a significant antinociceptive effect both in the acute and inflammatory phases of the test. Although Valorphin hexa-, hepta-, and octapeptide analogs demonstrated a significant antinociceptive effect, they showed substantial differences considering their effective dose and the phase of the test as compared to the Valorphin.
DISCUSSION
Data showed that modified heptapeptides pVV-H and pLV-H exerted the same or better antinociception in acute and inflammatory pain, in comparison to the reference peptide, while pL-H and pLVV-H analogues were less effective.
CONCLUSION
Our study contributes to the elucidation of the role of Valine and the number of amino acid residues in the structure of hemorphin peptide analogs in their effectiveness in suppressing both acute and inflammatory experimental pain.
Identifiants
pubmed: 32798365
pii: PPL-EPUB-109102
doi: 10.2174/0929866527666200813200714
doi:
Substances chimiques
Analgesics
0
Hemoglobins
0
Peptide Fragments
0
VV-hemorphin-5
0
Formaldehyde
1HG84L3525
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
442-449Subventions
Organisme : Sofia University “St. Kliment Ohridski”
ID : 80-10-191/2019
Informations de copyright
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.