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Synthesis & Biological Evaluation of PYY(3–36) Analogs Substituted with Alanine

  • John S. Ahn
  • Ramina Nazarbaghi
  • Lawrence J. D'Souza
  • Soumitra Ghosh
  • Carolyn M. Jodka
  • Aung N. Lwin
  • Odile E. Levy
Part of the Advances in Experimental Medicine and Biology book series (volume 611)

Introduction

PYY is a 36-residue peptide first isolated from porcine intestine (Figure 1) [ 1, 2]. Two endogenous forms of PYY, PYY(1-36) and the post-DPPIV [ 3, 4] activated PYY(3-36), are released into the circulation following a meal [ 1, 5]. PYY(3–36) appears to be the predominant secreted form. PYY has been known to inhibit gastric, [ 6] pancreatic and intestinal secretions [ 7]. PYY binds and activates at least four receptor subtypes (Y 1, Y 2, Y 4 and Y 5) [ 8, 9, 10] in rats and humans. These Y receptor subtypes display different patterns of affinity and activation for PYY, PYY(3–36) and synthetically modified PYY analogs. PYY(3–36) is a selective ligand for Y 2 and Y 5 receptors, implicated in food intake and feeding behavior, respectively [ 11]. In this study, PYY(3–36) analogs, where each residue of the natural sequence is replaced by L-alanine, and analogs with multiple alanine substitutions were synthesized. The three alanines at positions 7, 12 and 22 were replaced by a D-alanine. The...

Keywords

Molecular Entity Intestinal Secretion Alanine Substitution Receptor Binding Assay Equimolar Dose 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • John S. Ahn
    • 1
  • Ramina Nazarbaghi
    • 1
  • Lawrence J. D'Souza
    • 1
  • Soumitra Ghosh
    • 1
  • Carolyn M. Jodka
    • 1
  • Aung N. Lwin
    • 1
  • Odile E. Levy
    • 1
  1. 1.Amylin Pharmaceuticals, Inc.San DiegoUSA

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