Biological properties of a new fluorescent biphalin fragment analogue.
Previous studies of structure-activity of biphalin defined fragments which expressed the full biological potency of the parent compound. The most simple fragment was Tyr-D-Ala-Gly-Phe-NH-NH<--X, where X=Phe, but it also could be other hydrophobic amino acids. This paper presents data that replacement of the phenylalanine with a dansyl (X=DNS) groups gives an analogue (AA2016) that fully preserves the high affinity of the initial analogue for both mu and delta opioid receptors. In the tail flick test in rats, intrathecal injection of the compound produces strong antinociception, comparable to the parent biphalin. Because AA2016 contains a strong fluorescent group, it can be a very useful tool for prospective studies in vivo, including biological barrier permeability, tissue distribution, metabolism and receptor-ligand complex formation.
Lipkowski
Andrzej W
AW
Department of Chemistry, University of Arizona, Tucson 85721, USA.
Misicka
Aleksandra
A
Kosson
Dariusz
D
Kosson
Piotr
P
Lachwa-From
Magdalena
M
Brodzik-Bienkowska
Agnieszka
A
Hruby
Victor J
VJ
D000698:Analgesia; D000700:Analgesics / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D003619:Dansyl Compounds; D004745:Enkephalins / Q000138:chemical synthesis / Q000494:pharmacology*; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000494:pharmacology*; D008297:Male; D010146:Pain / Q000188:drug therapy / Q000378:metabolism; D010649:Phenylalanine; D051381:Rats; D017208:Rats, Wistar; D017465:Receptors, Opioid, delta / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000378:metabolism
D000700:Analgesics; D003619:Dansyl Compounds; D004745:Enkephalins; D005456:Fluorescent Dyes; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D010649:Phenylalanine; C053673:biphalin