Wydział Chemii

Anna Adamska

Alicja Kluczyk

Maria Camilla Cerlesi

Girolamo Calò

Anna Janecka

Attila Borics

2016

Bioorganic and Medicinal Chemistry

24

1582-1588

10.1016/j.bmc.2016.02.034

Naukowa

Angielski

Artykuł

Morphiceptin (Tyr-Pro-Phe-Pro-NH2), a tetrapeptide amide, is a selective ligand of the l-opioid receptor
(MOR). This study reports the synthesis and biological evaluation of a series of novel morphiceptin analogs
modified in positions 2 or/and 4 by introduction of 4,4-difluoroproline (F2Pro) in L or D configuration.
Depending on the fluorinated amino acid configuration and its position in the sequence, new analogs
behaved as selective full MOR agonists showing high, moderate, or relatively low potency. The most
potent analog, Tyr-F2Pro-Phe-D-F2Pro-NH2, was also able to activate the j-opioid receptor (KOR),
although with low potency. Docking studies and the comparison of results with the high resolution crystallographic
structure of a MOR-agonist complex revealed possible structure–activity relationships of this
compound family.

solid-phase peptide synthesis, binding studies, opioid receptors, hot-late test, gastrointestinal transit, molecular dynamics, docking

http://dx.doi.org/10.1016/j.bmc.2016.02.034

http://www.elsevier.com