Myotropic effects of new proctolin analogues modified in the position 5 of peptide chain in insects.
To explain the role of the Thr5 residue of proctolin (Arg-Tyr-Leu-Pro-Thr) in the myotropic activity of this insect neuropeptide, we synthesized two groups of its analogues: 1) Arg-Tyr-Leu-Pro-X-OH with X = Val (1), D-Val (2), Ile (3), D-Ile (4), Ala (5), D-Ala (6), Asn (7), Gln (8), Ser (9), Pro (10), Phe (11), Asp (12), Glu (13), Arg (14), D-Arg (15), Lys (16) and Gly (17) and 2) Arg-Tyr-Leu-Pro-R', where R' = isobutylamine (18), S-1-methyl-1-phenylmethylamine (19), R-1-methyl-1-phenylmethylamine (20), R-2-amino-1-propanol (21), S-2-amino-1-propanol (22), R-1-amino-2-propanol (23), S-2-amino-1-propanol (24), 3-amino-1-propanol (25). Decapeptide proctolylproctolin (H-Arg-Tyr-Leu-Pro-Thr-Arg-Tyr-Leu-Pro-Thr-OH) (26) was synthesized. Syntheses of these peptides were carried out by solid-phase method. All peptides were bioassayed in vitro on the semi-isolated hearts of Tenebrio molitor using a cardioexcitatory test and on the foregut of locust (Schistocerca gregaria). Peptides 1, 3, 5, 9, 13, 14, 16, 22, and 23 retained about 30-50% of the cardioexcitatory activity in T. molitor. Analogues 1 and 3 preserved about 50% and analogue 8 about 80% of the myotropic activity, whereas compound 4 and 9 showed a very weak contractile activity in S. gregaria.
Szeszel-Fedorowicz
W
W
Faculty of Chemistry, University of Wrocław, Poland.
Rosiński
G
G
Issberner
J
J
Osborne
R
R
Sliwowska
J
J
Konopińska
D
D
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006110:Grasshoppers / Q000187:drug effects / Q000502:physiology; D006321:Heart / Q000187:drug effects; D007313:Insecta / Q000737:chemistry*; D007422:Intestines / Q000187:drug effects / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects*; D009479:Neuropeptides; D018377:Neurotransmitter Agents / Q000737:chemistry / Q000494:pharmacology; D009842:Oligopeptides / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013712:Tenebrio / Q000187:drug effects / Q000502:physiology
D009479:Neuropeptides; D018377:Neurotransmitter Agents; D009842:Oligopeptides; C011536:proctolin