Tetrahydroisoquinoline derivatives of enkephalins: synthesis and properties.
Tetrahydroisoquinolines (TIQs) are endogenous alkaloid compounds deriving from the non-enzymatic Pictet-Spengler condensation of catecholamines with aldehydes. These compounds are able to unsettle catecholamines uptake and release from synaptosomes and have been detected in urine and in post-mortem Parkinsonian brains. We have obtained in vitro, by the reaction of dopa-enkephalin (dopa-Gly-Gly-Phe-Leu) with acetaldehyde in the presence of rameic ions, a TIQ derivative of Leu-enkephalin. The isolation and the recovery of the peptide was obtained by HPLC. The acid hydrolysis and the subsequent analysis of the peptide lysate by the Amino acid analyser clearly revealed the absence of dopa, while the electrospray ionisation mass spectrometry showed that the sequence of the enkephalin derivative was the following: 3-carboxy-salsolinol-Gly-Gly-Phe-Leu (TIQ-enkephalin). This compound was not a good substrate for microsomal aminopeptidase and pronase with respect to Leu-enkephalin. Tested in the binding assay, the TIQ-enkephalin exhibited a very poor affinity toward the enkephalin receptors. When the TIQ-enkephalin was incubated with tyrosinase or peroxidase/H(2)O(2), the formation of TIQ-opio-melanins occurred.
Foppoli
Cesira
C
CNR Centre of Molecular Biology c/o University La Sapienza, Piazza le Aldo Moro 5, 00185 Rome, Italy.
Coccia
Raffaella
R
Blarzino
Carla
C
Cini
Chiara
C
Rosei
Maria Anna
MA
D001665:Binding Sites; D002851:Chromatography, High Pressure Liquid; D004745:Enkephalins / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D006868:Hydrolysis; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D010084:Oxidation-Reduction; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*; D012490:Salsoline Alkaloids / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization; D044005:Tetrahydroisoquinolines
C459400:3--carboxysalsolinol-Gly-Gly-Phe-Leu; D004745:Enkephalins; D007546:Isoquinolines; D011957:Receptors, Opioid; D012490:Salsoline Alkaloids; D044005:Tetrahydroisoquinolines; C011704:carboxysalsolinol; C014843:1,2,3,4-tetrahydroisoquinoline