A novel cis-peptide bond motif inducing beta-turn type VI. The synthesis of enkephalin analogues modified with 4-aminopyroglutamic acid.
A new pathway leading to a mixture of four isomers of 4-aminopyroglutamic acid is described. Michael type addition of Z-deltaAla-OMe to enolates prepared from acylaminomalonates, followed by hydrolysis and decarboxylation give protected 4-aminopyroglutamic acid with the cis:trans ratio approximately 3:2. This mixture was incorporated into Leu-enkephalin (position 2-3). After separation of peptides it appeared that all analogues were essentially inactive in guinea pig ileum and mouse vas deferens bioassays.
Kaczmarek
K
K
Institute of Organic Chemistry, Technical University of Lódź, Poland.
Kaleta
M
M
Chung
N N
NN
Schiller
P W
PW
Zabrocki
J
J
D020816:Amino Acid Motifs; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004745:Enkephalins / Q000737:chemistry* / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000378:metabolism; D020128:Inhibitory Concentration 50; D008297:Male; D051379:Mice; D008956:Models, Chemical; D010455:Peptides / Q000737:chemistry*; D011761:Pyrrolidonecarboxylic Acid / Q000737:chemistry*; D013237:Stereoisomerism; D014649:Vas Deferens / Q000378:metabolism
D004745:Enkephalins; D010455:Peptides; D011761:Pyrrolidonecarboxylic Acid