Syntheses of potent Leu-enkephalin analogs possessing beta-hydroxy-alpha,alpha-disubstituted-alpha-amino acid and their characterization to opioid receptors.
Novel Leu-enkephalin (Leu-Enk) (1) analogs possessing various types of alpha-substituted serine instead of its glycine residue in the position 2 were synthesized via an efficient O,N-migration method. The binding characteristics of the synthetic analogs using Chinese hamster ovary (CHO) cells expressed cloned rat mu-, delta-, and kappa-receptors revealed that [(1R,2S)-Ahh2]Enk (7) was the most potent agonist of delta-opioid receptors among all the synthetic analogs tested, and was 10 times more potent than the native Leu-Enk.
Horikawa
M
M
Suntory Institute for Bioorganic Research, Osaka, Japan.
Shigeri
Y
Y
Yumoto
N
N
Yoshikawa
S
S
Nakajima
T
T
Ohfune
Y
Y
D000596:Amino Acids / Q000737:chemistry*; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D000242:Cyclic AMP / Q000096:biosynthesis; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011957:Receptors, Opioid / Q000819:agonists* / Q000737:chemistry / Q000378:metabolism
D000596:Amino Acids; D011957:Receptors, Opioid; D004743:Enkephalin, Leucine; D000242:Cyclic AMP