Novel L-prolyl-L-leucylglycinamide (PLG) tripeptidomimetics based on a 2-azanorbornane scaffold as positive allosteric modulators of the D2R

• Type: Article in International Scientific Journal
• Date: 2016

Authors

Sampaio Dias, IE (Author) Other; Sousa, CAD (Author) Other; Garcia Mera, X (Author) Other; da Costa, JF (Author) Other; Caamano, O (Author) Other; Rodriguez Borges, JE (Author) FCUP

Journal

Title: Organic and Biomolecular Chemistry

Vol. 14

Pages: 11065-11069

ISSN: 1477-0520

Publisher: Royal Society of Chemistry

Indexing

ISI Web of Knowledge - 12 Citations

Scopus - 12 Citations

Other information

Authenticus ID: P-00M-B4W

DOI: 10.1039/c6ob02248k

Abstract (EN): An efficient and straightforward orthogonal methodology was successfully developed to achieve constrained L-prolyl-L-leucylglycinamide (PLG) analogues starting from two proline mimetics based on a 2-azanorbornane scaffold. A preliminary dopamine D-2 receptor radiolabeled binding assay with [H-3]-N-propylnorapomorphine shows that enantiopurity of PLG peptidomimetics based on 2-azanorbornane is a requirement to achieve statistically significant positive modulators of the D-2 receptor. This is the first documented active peptidomimetic of PLG whose bioactivity is not correlated with the C-terminal carboxamide pharmacophore and which cannot adopt the hypothesized type II beta-turn conformation.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 5