Synthesis and biological evaluation of a novel pyroglutamyl-modified TRH analogue.
The TRH analogue 3, incorporating the (S)-isothiazolidine-1,1-dioxide-3-carboxylic acid (1) moiety in place of the native L-pyroglutamic acid (pGlu) residue, has been synthesized and fully characterized by 1H and 13C NMR. The effects of replacing pGlu with its sulphonamido counterpart on biological activity have been investigated. This peptide, which is significantly stabilized towards hydrolysis by pyroglutamyl peptidase type I (PP I, EC 3.4.19.3), has shown to maintain in vitro prolactin-releasing activity.
Brunetti
L
L
Dipartimento di Scienze del Farmaco, Università degli Studi G D'Annunzio, Chieti, Italy.
Cacciatore
I
I
Di Stefano
A
A
Duprè
S
S
Giorgi
A
A
Luisi
G
G
Michelotto
B
B
Orlando
G
G
Pinnen
F
F
Recinella
L
L
Sozio
P
P
Spirito
A
A
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008297:Male; D019906:Nuclear Magnetic Resonance, Biomolecular; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism; D011751:Pyroglutamyl-Peptidase I / Q000378:metabolism; D011761:Pyrrolidonecarboxylic Acid / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
D013973:Thyrotropin-Releasing Hormone; D011388:Prolactin; D011751:Pyroglutamyl-Peptidase I; D011761:Pyrrolidonecarboxylic Acid; D004298:Dopamine