Double-enkephalins—Synthesis, activity on guinea-pig ileum, and analgesic effect

Novel Cyclic Biphalin Analogue with Improved Antinociceptive Properties

“…1,2 Its noticeable bioactivity is due to the peculiar structure, which has the ability to match the topographical requirements for both μ and δ opioid receptors. 3−5 Furthermore, this opioid octapeptide induces less physical dependence and toxicities than other opioids.…”

New Dimeric Tetrapeptide Enkephalin AnaloguesHydrophilic Spacer Length and Configuration Affects Potency and Receptor Selectivity

“…Semipreparative HPLC was perform ed on a Supelco LC-18-DB reverse phase column with linear gradients of buffer A (0.03 M ammonium acetate, pH 5.0) and buffer B (33% buffer A/67% acetonitrile, v/v) and monitoring at 230 or 260 nm. (3) were prepared according to known procedures [14][15][16] from l,3-dichloro-2-propanol [17], l^-dichloro-l^-dideoxy-m eso-erythritol [18] and D -tartaric acid, respectively. Their 13C NMR chemical shifts are given in Table I. 2 (6) were prepared from appro Table 1.13C NMR data assignments for characteristic carbon atoms in intermediates: 1 -6 ,7 a, 8 a and 9 a (<5 in ppm).…”

“…The analo gues exhibited generally high selectivity for < 5 recep tors, and the authors suggested that such dimers could serve as bivalent ligands binding simulta neously to two distinct but closely clustered < 5 recep tors. Lipkowski et al [3,9] have shown that even a shorter bivalent enkephalin analogue with a dihydrazide bond possessed relatively high activity and also <5 receptor selectivity.…”

“…Analogues called dimeric [4,5], double [3] or bivalent [8] enkephalins which contain bridges of various type and length between two active peptide fragm ents belong to this class of compounds. The nature of a bridge can alter, both, biological activi ty and selectivity toward opioid receptors of an analogue due to increase of enzymatic resistance and possibility of simultaneous interaction with two re ceptor sites.…”

“…O ne of the promising possibility of developing new opioid analogues is the synthesis of compounds containing two pharmacophores in one molecule [1][2][3][4][5][6][7]. Analogues called dimeric [4,5], double [3] or bivalent [8] enkephalins which contain bridges of various type and length between two active peptide fragm ents belong to this class of compounds.…”