PMID: 9178348Mar 26, 1997Paper

N-terminal modifications to AKH-I from Locusta migratoria: assessment of biological potencies in vivo and in vitro

Regulatory Peptides
M J LeeG Goldsworthy

Abstract

To investigate the receptor tolerances to N-terminal variation, novel analogues to Locusta AKH-I (adipokinetic hormone) have been synthesized with modifications at the N-terminus. Analogues were made where the N-terminal pyroglutamyl residue was spaced further from the remainder of the molecule by the insertion of glycine residues between either pGlu1 and Leu2 (Gly1a-AKH-I, or Leu2 and Asn3 (Gly2a-AKH-I and Gly2ab-AKH-I). Other modified hormones with N-terminal extensions were: (Ahx)n-AKH-I (Ahx. aminohexanoic acid); HPP(Ahx)n-AKH-I (HPP. hydroxyphenyl propionate) and Ac(Ahx)n-AKH-I (where n = 0-3). Finally, acetylated and non-acetylated amino acids were substituted for pGlu1: Glu, Pro, Ala and Tyr. The effects of these modifications on biological potency were tested in the lipid mobilization assay in vivo and acetate uptake assay in vitro. The potency of AKH-I was reduced much more by insertion of glycine between pGlu1 and Leu2, than between Leu2 and Asn3, perhaps suggesting that a hydrophobic residue is required adjacent to the pGlu for biological activity. In addition, a residue N-terminal to Leu2 is necessary for activity (i.e., [despGlu]-AKH-I is inactive) unless the free N-terminus is acetylated: Ac[despGlu]-AKH-I is acti...Continue Reading

References

Aug 1, 1979·Hoppe-Seyler's Zeitschrift für physiologische Chemie·M ChristensenL Josefsson
Jan 1, 1991·Archives of Insect Biochemistry and Physiology·R ZieglerJ H Law
Jan 1, 1985·Peptides·W MordueK J Siegert
Aug 1, 1985·Biological Chemistry Hoppe-Seyler·K SiegertW Mordue
Jan 1, 1996·Journal of Comparative Physiology. B, Biochemical, Systemic, and Environmental Physiology·M J Lee, G J Goldsworthy
Aug 6, 1996·Proceedings of the National Academy of Sciences of the United States of America·R C OudejansD J Van der Horst
Aug 1, 1997·Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology·G J GoldsworthyD Hyde

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Citations

Aug 1, 1997·Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology·G J GoldsworthyD Hyde
Jul 19, 2000·Insect Biochemistry and Molecular Biology·M J LeeG J Goldsworthy
Nov 9, 2016·General and Comparative Endocrinology·Marie-Pierre DubosPascal Favrel

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