1.Synthesis, biological activity, and conformational study of N-methylated allatostatin analogues inhibiting juvenile hormone biosynthesis.
Xie Y1,2,3, Zhang L1, Zhang C1, Wu X1,2, Deng X1, Yang X1, Tobe SS2. J Agric Food Chem. 2015 Mar 25;63(11):2870-6. doi: 10.1021/acs.jafc.5b00882. Epub 2015 Mar 13.
An allatostatin (AST) neuropeptide mimic (H17) is a potential insect growth regulator, which inhibits the production of juvenile hormone (JH) by the corpora allata. To determine the effect of conformation of novel AST analogues and their ability to inhibit JH biosynthesis, eight insect AST analogues were synthesized using H17 as the lead compound by N-methylation scanning, which is a common strategy for improving the biological properties of peptides. A bioassay using JH production by corpora allata of the cockroach Diploptera punctata indicated that single N-methylation mimics (analogues 1-4) showed more activity than double N-methylation mimics (analogues 5-8). Especially, analogues 1 and 4 showed roughly equivalent activity to that of H17, with IC50 values of 5.17 × 10(-8) and 6.44 × 10(-8) M, respectively. Molecular modeling based on nuclear magnetic resonance data showed that the conformation of analogues 1 and 4 seems to be flexible, whereas analogues 2 and 3 showed a type IV β-turn.
2.Probing the active conformation of FGLamide allatostatin analogs with N-terminal modifications using NMR spectroscopy and molecular modeling.
Xie Y1, Zhang L2, Wu XQ2, Zhang CL2, Yang XL3, Tobe SS4. Peptides. 2015 Jun;68:214-8. doi: 10.1016/j.peptides.2014.06.015. Epub 2014 Jul 8.
The FGLamide allatostatins (ASTs) can inhibit the production of juvenile hormone in vitro, and they therefore are regarded as possible insect growth regulator candidates for pest control. To understand the structural features of the ASTs that cause the differences in their activity the pentapeptide and four N-terminal modifications of AST analogs (H17, K9, K10 and K23) were selected to investigate their conformations. From NMR spectroscopy and molecular modeling, it is clear that K23 and K9 have a type IV β-turn and a γ turn in DMSO, respectively. The pentapeptide, H17 and K10 form a flexible conformation. Our study indicates that this flexible conformation could be an important and indispensable structural element for activity, whereas the turn structure may not be especially significant for biological activity.
3.Effect of allatostatin and proctolin on antennal pulsatile organ and hindgut muscle in the cockroach, Diploptera punctata.
Lange AB1, Chan KK, Stay B. Arch Insect Biochem Physiol. 1993;24(2):79-92.
Diploptera punctata allatostatins are brain neuropeptides that inhibit juvenile hormone synthesis by corpora allata. They also occur in nerves of many organs other than corpora allata. The distribution of allatostatins in, and the effect of allatostatins on two other organs, antennal pulsatile organ and hindgut, are demonstrated here. Allatostatin I-like immunoreactive material is present in cells of subesophageal and terminal abdominal ganglia; these ganglia are known to contain the cells that project to antennal heart nerve and proctodeal nerve, respectively. Electron micrographs of both organs show nerve terminals with allatostatic immunoreactive granules along with terminals containing nonimmunoreactive granules. Immunoreactive neurosecretory granules are about 200 nm in largest dimension. In the antennal pulsatile organ, profiles of the nerve terminals are larger in the ampullar wall than in the muscle; in hindgut the terminals with immunoreactive granules are associated with the muscle net below the circular muscle.
4.Neural substrate and allatostatin-like innervation of the gut of Locusta migratoria.
Robertson L1, Lange AB. J Insect Physiol. 2010 Aug;56(8):893-901. doi: 10.1016/j.jinsphys.2010.05.003. Epub 2010 May 14.
Allatostatin-like immunoreactivity (ALI) is widely distributed in processes and varicosities on the fore-, mid-, and hindgut of the locust, and within midgut open-type endocrine-like cells. ALI is also observed in cells and processes in all ganglia of the central nervous system (CNS) and the stomatogastric nervous system (SNS). Ventral unpaired median neurons (VUMs) contained ALI within abdominal ganglia IV-VII. Neurobiotin retrograde fills of the branches of the 11th sternal nerve that innervate the hindgut revealed 2-4 VUMs in abdominal ganglia IV-VIIth, which also contain ALI. The VIIIth abdominal ganglion contained three ventral medial groups of neurons that filled with neurobiotin and contained ALI. The co-localization of ALI in the identified neurons suggests that these cells are the source of ALI on the hindgut. A retrograde fill of the nerves of the ingluvial ganglia that innervate the foregut revealed numerous neurons within the frontal ganglion and an extensive neuropile in the hypocerebral ganglion, but there seems to be no apparent co-localization of neurobiotin and ALI in these neurons, indicating the source of ALI on the foregut comes via the brain, through the SNS.
