Transformation of Pro-Leu-Gly-NH2 peptidomimetic positive allosteric modulators of the dopamine D2 receptor into negative modulators

Swapna Bhagwanth, Satyendra Mishra, Ritesh Daya, Jordan Mah, Ram K. Mishra, Rodney L. Johnson

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

The synthesis of dimethyl derivatives of 5.6.5 spiro bicyclic lactam Pro-Leu-Gly-NH2 peptidomimetics was carried out to test the hypothesis that by placing methyl groups on the β-methylene carbon of the thiazolidine ring steric bulk would be introduced into the topological space that the β-methylene carbon is believed to occupy in the negative allosteric modulators of the dopamine D2 receptor. With such a modification, a positive allosteric modulator would be converted into a negative allosteric modulator. This hypothesis was shown to be correct as 3a and 4a where found to be negative allosteric modulators, whereas their unmethylated derivatives were positive allosteric modulators of the dopamine D2 receptor. (Chemical Equation Presented).

Original languageEnglish (US)
Pages (from-to)274-284
Number of pages11
JournalACS Chemical Neuroscience
Volume3
Issue number4
DOIs
StatePublished - Apr 18 2012

Keywords

  • Allosteric modulation
  • Dopamine D receptor
  • Peptidomimetic
  • Pro-Leu-Gly-NH
  • Spiro bicyclic lactam

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