Acyl, pseudotetra-, tri- and dipeptide active-core analogs of insect neuropeptides.
Pseudopeptides of the achetakinin insect neuropeptide family were synthesized by replacing the amino acid blocks Phe-, Phe-Tyr-, and Phe-Tyr-Pro- of the active-core pentapeptide Phe-Tyr-Pro-Trp-Gly-NH2 with hydrocinnamic acid, 6-phenylhexanoic acid, and both 9-phenylnonanoic and 6-phenylhexanoic acid, respectively. All four of these analogs retained myotropic activity, demonstrating that the active core could be reduced from a pentapeptide to a modified dipeptide. Most notable of these was the pseudotetrapeptide hydrocinnamyl-Tyr-Pro-Trp-Gly-NH2, which retained 70% of the potency and over 85% of the maximal activity of the parent pentapeptide. The N-terminal amino group, the phenol ring of the Tyr residue, the sulfate moiety and the Gly residue of the insect sulfakinin active core Tyr(SO3H)-Gly-His-Met-Arg-Phe-NH2 were all replaced by dodecanedioic acid. The resulting pseudotetrapeptide, dodecandioyl-His-Nle-Arg-Phe-NH2, elicited myostimulatory activity. Conversely, the related acyl pseudopentapeptide azelayl-Gly-His-Nle-Arg-Phe-NH2 proved myoinhibitory. A possible explanation for these disparate biological responses is discussed. These acyl pseudopeptides are important advances towards the eventual development of stable, potent mimetic agonists and antagonists of insect neuropeptides.
Nachman
R J
RJ
United States Department of Agriculture, Agricultural Research Service, College Station, Texas.
Holman
G M
GM
Hayes
T K
TK
Beier
R C
RC
D000595:Amino Acid Sequence; D000818:Animals; D007313:Insecta / Q000737:chemistry*; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009479:Neuropeptides / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry*; D013431:Sulfates / Q000737:chemistry
D009479:Neuropeptides; D009842:Oligopeptides; D013431:Sulfates; C079230:achetakinin