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A Short-Length Peptide YY Analogue with Anorectic Effect in Mice
[Image: see text] Peripheral administration of PYY(3–36), a fragment of peptide YY (PYY), has been reported to reduce food intake by activating the neuropeptide Y2 receptor (Y2R). An N-terminally truncated PYY analogue, benzoyl-[Ala(26),Ile(28,31)]PYY(25–36) (1), showed a relatively potent agonist a...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2017
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6044503/ https://www.ncbi.nlm.nih.gov/pubmed/30023658 http://dx.doi.org/10.1021/acsomega.7b00258 |
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author | Nishizawa, Naoki Niida, Ayumu Masuda, Yasushi Kumano, Satoshi Yokoyama, Kotaro Hirabayashi, Hideki Amano, Nobuyuki Ohtaki, Tetsuya Asami, Taiji |
author_facet | Nishizawa, Naoki Niida, Ayumu Masuda, Yasushi Kumano, Satoshi Yokoyama, Kotaro Hirabayashi, Hideki Amano, Nobuyuki Ohtaki, Tetsuya Asami, Taiji |
author_sort | Nishizawa, Naoki |
collection | PubMed |
description | [Image: see text] Peripheral administration of PYY(3–36), a fragment of peptide YY (PYY), has been reported to reduce food intake by activating the neuropeptide Y2 receptor (Y2R). An N-terminally truncated PYY analogue, benzoyl-[Ala(26),Ile(28,31)]PYY(25–36) (1), showed a relatively potent agonist activity for Y2R but a weak anorectic activity by intraperitoneal administration (2000 nmol/kg) in lean mice because of its markedly poor biological stability in the mouse serum. Notably, two cyclohexylalanine (Cha) substitutions for Tyr residues at positions 27 and 36 (4) improved the stability in the mouse serum concomitant with enhanced anorectic activity. Further optimization at positions 27, 28, 30, and 31 revealed that 21, containing Cha(28) and Aib(31) residues, showed a more potent anorectic activity than PYY(3–36) at a low dose of 300 nmol/kg. The minimum effective dose by intraperitoneal administration of 21 was 30 nmol/kg (ca. 52 μg/kg) in mice, suggesting the biologic potential of short-length PYY(3–36) analogues with a potent anorectic effect. |
format | Online Article Text |
id | pubmed-6044503 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-60445032018-07-16 A Short-Length Peptide YY Analogue with Anorectic Effect in Mice Nishizawa, Naoki Niida, Ayumu Masuda, Yasushi Kumano, Satoshi Yokoyama, Kotaro Hirabayashi, Hideki Amano, Nobuyuki Ohtaki, Tetsuya Asami, Taiji ACS Omega [Image: see text] Peripheral administration of PYY(3–36), a fragment of peptide YY (PYY), has been reported to reduce food intake by activating the neuropeptide Y2 receptor (Y2R). An N-terminally truncated PYY analogue, benzoyl-[Ala(26),Ile(28,31)]PYY(25–36) (1), showed a relatively potent agonist activity for Y2R but a weak anorectic activity by intraperitoneal administration (2000 nmol/kg) in lean mice because of its markedly poor biological stability in the mouse serum. Notably, two cyclohexylalanine (Cha) substitutions for Tyr residues at positions 27 and 36 (4) improved the stability in the mouse serum concomitant with enhanced anorectic activity. Further optimization at positions 27, 28, 30, and 31 revealed that 21, containing Cha(28) and Aib(31) residues, showed a more potent anorectic activity than PYY(3–36) at a low dose of 300 nmol/kg. The minimum effective dose by intraperitoneal administration of 21 was 30 nmol/kg (ca. 52 μg/kg) in mice, suggesting the biologic potential of short-length PYY(3–36) analogues with a potent anorectic effect. American Chemical Society 2017-05-18 /pmc/articles/PMC6044503/ /pubmed/30023658 http://dx.doi.org/10.1021/acsomega.7b00258 Text en Copyright © 2017 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes. |
spellingShingle | Nishizawa, Naoki Niida, Ayumu Masuda, Yasushi Kumano, Satoshi Yokoyama, Kotaro Hirabayashi, Hideki Amano, Nobuyuki Ohtaki, Tetsuya Asami, Taiji A Short-Length Peptide YY Analogue with Anorectic Effect in Mice |
title | A Short-Length
Peptide YY Analogue with Anorectic Effect in Mice |
title_full | A Short-Length
Peptide YY Analogue with Anorectic Effect in Mice |
title_fullStr | A Short-Length
Peptide YY Analogue with Anorectic Effect in Mice |
title_full_unstemmed | A Short-Length
Peptide YY Analogue with Anorectic Effect in Mice |
title_short | A Short-Length
Peptide YY Analogue with Anorectic Effect in Mice |
title_sort | short-length
peptide yy analogue with anorectic effect in mice |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6044503/ https://www.ncbi.nlm.nih.gov/pubmed/30023658 http://dx.doi.org/10.1021/acsomega.7b00258 |
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