New 2 ',6 '-dimethyl-L-tyrosine (Dmt) opioid peptidomimetics based on the Aba-Gly scaffold. Development of unique mu-opioid receptor ligands

The Aba-Gly scaffold, incorporated into Dmt-Tic ligands ( H-Dmt-Tic-Gly-NH-CH2-Ph,H-Dmt-Tic-Gly-NH-Ph, H-Dmt-Tic-NH-CH2-Bid), exhibited mixed mu/delta or delta opioid receptor activities with A agonism. Substitution of Tic by Aba-Gly coupled to -NH-CH2-Ph ( 1), -NH-Ph ( 2), or -Bid ( Bid) 1H-benzimidazole-2-yl) ( 3) shifted affinity ( Ki( mu)) 0.46, 1.48, and 19.9 nM, respectively), selectivity, and bioactivity to mu-opioid receptors. These compounds represent templates for a new class of lead opioid agonists that are easily synthesized and suitable for therapeutic pain relief