p-Nitrophenoxycarbonyl derivatives of Boc-protected diaminoalkanes in the synthesis of enkephalin peptidomimetics.
The synthesis of p-nitrophenoxycarbonyl derivatives of 1-Boc-1,2-diaminoethane, 1-Boc-1,3-diaminopropane and 1-Boc-1,4-diaminobutane is described. These derivatives were used to synthesize five peptidomimetics, analogues of enkephalin, containing alkylurea units inside the peptide chain and at the C-terminal. All syntheses were carried out in solid phase on MBHA resin. Peptidomimetics with alkylurea units inserted into the peptide chain were synthesized using the standard method employing the Boc-strategy, with TFA deprotection and HF cleavage. The analogue containing a C-terminal alkylurea unit was synthesized using the Boc-strategy, with HCl/dioxane deprotection and TFA cleavage. All of the analogues were examined for opioid activity in GPI and MVD assays. The activity of the analogue containing a C-terminal alkylurea unit was comparable to that of [Leu5]-enkephalin, while the other analogues were less active.
Wiszniewska
Anna
A
Department of Chemistry, Warsaw University, Pasteura 1, Warsaw, 02-093, Poland.
Kunce
Danuta
D
Chung
Nga N
NN
Schiller
Peter W
PW
Izdebski
Jan
J
D000473:Alkanes / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D004745:Enkephalins / Q000138:chemical synthesis*; D018716:Molecular Mimicry; D021241:Spectrometry, Mass, Electrospray Ionization
D000473:Alkanes; D004745:Enkephalins