Issue 47, 2016

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

Abstract

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 D2 receptor radiolabeled binding assay with [3H]-N-propylnorapomorphine shows that enantiopurity of PLG peptidomimetics based on 2-azanorbornane is a requirement to achieve statistically significant positive modulators of the D2 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 β-turn conformation.

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

Supplementary files

Article information

Article type
Communication
Submitted
14 Oct 2016
Accepted
03 Nov 2016
First published
03 Nov 2016

Org. Biomol. Chem., 2016,14, 11065-11069

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

I. E. Sampaio-Dias, C. A. D. Sousa, X. García-Mera, J. Ferreira da Costa, O. Caamaño and J. E. Rodríguez-Borges, Org. Biomol. Chem., 2016, 14, 11065 DOI: 10.1039/C6OB02248K

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