Alytesin

[Amphibian bombesin and its analog alytesin].[Pubmed:2783173]

Bioorg Khim. 1989 Jun;15(6):748-62.

A convenient route of synthesis of amphibian bombesin and bombesin-like peptide Alytesin was found. These tetradecapeptides were obtained by assembling the 1-5 and 6-14 fragments by means of DCC-HONB or mixed anhydrides methods. Structure of the tetradecapeptides was confirmed by high resolution NMR spectroscopy data. The bombesin and Alytesin synthesized potently decrease body temperature and stimulate pancreatic juice secretion.

Central and peripheral alytesin cause short-term anorexigenic effects in neonatal chicks.[Pubmed:18384875]

Neuropeptides. 2008 Jun;42(3):283-91.

We studied the effects of Alytesin, a natural analogue of bombesin, on appetite-related responses and behaviors in neonatal chicks. Chicks responded to both intracerebroventricular (ICV) and peripheral injections of Alytesin with short-term reduced feed intake. ICV Alytesin caused reduced short-term water intake when feed was present, but we determined this effect was secondary to feed intake since an effect on water intake was not detected in feed-restricted Alytesin-treated chicks. The anorexigenic effect of both ICV and peripheral Alytesin may be mediated at the hypothalamus, since all hypothalamic nuclei studied; regio lateralis hypothalami, nucleus dorsomedialis hypothalami, nucleus paraventricularis magnocellularis, nucleus perventricularis hypothalami, nucleus infundibuli hypothalami and the nucleus ventromedialis hypothalami, were activated as evident by increased c-Fos immunoreactivity. Central Alytesin did not cause increased behaviors that were unrelated to ingestion and did not cause anxiety-related behavior patterns. Additionally, central Alytesin did not affect pecking efficacy. We conclude that both ICV and peripheral Alytesin injections induce anorexigenic effects in chicks, and the hypothalamus is involved. While the anorexigenic effects of Alytesin and bombesin appear to be conserved across species, the two peptides may differ in other behavioral responses and central mechanisms of action.

Antimicrobial peptides and alytesin are co-secreted from the venom of the Midwife toad, Alytes maurus (Alytidae, Anura): implications for the evolution of frog skin defensive secretions.[Pubmed:22800568]

Toxicon. 2012 Nov;60(6):967-81.

The skin secretions of frogs and toads (Anura) have long been a known source of a vast abundance of bioactive substances. In the past decade, transcriptome data of the granular glands of anuran skin has given new impetus to investigations of the putative constituent peptides. Alytes obstetricans was recently investigated and novel peptides with antimicrobial activity were isolated and functionally characterised. However, genetic data for the evolutionarily ancient lineage to which Alytes belongs (midwife toads; Alytidae) remains unavailable. Here we present the first such genetic data for Alytidae, derived via the granular gland transcriptome of a closely-related species of midwife toad, Alytes maurus. First, we present nucleotide sequences of the entire peptide precursors for four novel antimicrobial peptides (AMPs). The two precursors resemble those from Bombinatoridae in both their structural architecture and amino acid sequence. Each precursor comprises two AMPs as tandem repeats, with a member of the alyteserin-1 family (alyteserin-1Ma: GFKEVLKADLGSLVKGIAAHVAN-NH2 or alyteserin-1Mb: GFKEVLKAGLGSLVKGIPAHVAN-NH2) followed by its corresponding member from the alyteserin-2 family (alyteserin-2Ma: FIGKLISAASGLLSHL-NH2 or alyteserin-2Mb: ILGAIIPLVSGLLSHL-NH2). Synthetic replicates of the four AMPs possessed minimal inhibitory concentrations (MICs) ranging from 9.5 to 300 muM, with the most potent being alyteserin-2Ma. Second, we also cloned the cDNA encoding an Alytesin precursor, with the active Alytesin exhibiting high sequence identity to bombesin-related peptides from other frogs. All putative mature peptide sequences were confirmed to be present in the skin secretion via LC/MS. The close structural resemblance of the alyteserin genes that we isolated for A. maurus with those of Bombina provide independent molecular evidence for a close evolutionary relationship between these genera as well as more support for the convergent evolution of the AMP system within anurans. In contrast to the more evolutionarily conserved nature of neuropeptides (including Alytesin, which we also isolated), the more variable nature of the AMP system together with the sporadic distribution of AMPs among anuran amphibians fuels in part our hypothesis that the latter system was co-opted secondarily to fulfil a function in the innate immune system, having originally evolved for defence against potential macropredators.

Bombesin, bombesin analogues, and related peptides: effects on thermoregulation.[Pubmed:656396]

Biochemistry. 1978 May 2;17(9):1766-71.

The synthesis and biological evaluation on thermoregulation of 39 peptides related to bombesin (structural analogues or other naturally occurring peptides) are described. The bioassay system reported measures the ability of peptides injected intracisternally to lower body temperature of cold (4 degrees C) exposed rats. The most potent analogues of bombesin were those in which positions one to five (not included) were altered, indicating that the decapeptide C terminal was sufficient for full potency. Gln at the seventh position and Gly at the 11th position could be replaced by D-Gln and D-Ala (but not D-Pro or D-Phe), respectively, without any change in potency. Methionine at the 14 position could be replaced with its D isomer with retention of 10% biological activity. Any other alteration of the C terminus (deletions or free acid with the exception of the N-methylamide) drastically reduced the biological potency of those peptides. Among other naturally occurring peptides, Alytesin was found to have 100% of bombesin potency whereas litorin, neurotensin, xenopsin, substance P, physalaemin, and eledoisin were found to be in the order of 10(4) times less potent. The shortest peptide found to have full biological activity is the octapeptide des-Glp-Gln-Arg-Leu-Gly-Asn[D-Glp7, D-Ala11]-bombesin.

Relative potency of bombesin-like peptides.[Pubmed:1201380]

Br J Pharmacol. 1975 Oct;55(2):221-7.

The pharmacological activity of two natural bombesin-like peptides, Alytesin and litorin, and 25 related synthetic peptides has been compared to that of bombesin. 2 The minimum length of the amino acid chain required for the first appearance of bombesin-like effects was represented by the C-terminal heptapeptide, and the minimum length for maximal effects by the C-terminal nonapeptide. The latter possessed approximately the same activity as bombesin and may be considered a good substitute. 3 Both the tryptophan and histidine residues seemed to be essential for bombesin-like activity. 4 The C-terminal octapeptide was less active than either bombesin or the C-terminal nonapeptide and its action was more rapid in onset and less sustained. 5 Litorin apparently has an intermediate position between bombesin octapeptide and bombesin nonapeptide in the speed and duration of its effects. The relationship between structure and activity is discussed.