An integrative description of Euscorpius diagorasi sp. n. from Rhodes, Greece (Scorpiones: Euscorpiidae)

  An integrative description of Euscorpius diagorasi sp. n. from Rhodes, Greece (Scorpiones: Euscorpiidae) Abstract The genus  Euscorpius  Thorell, 1876 comprises a diverse and taxonomically challenging group of scorpions in the Mediterranean, with Greece representing one of its principal centers of diversity. In this study, we provide an integrative description of  Euscorpius diagorasi   sp. n. , a new species from Rhodes Island, Greece. The new species is described on the basis of adult male and female morphology and mitochondrial COI sequence data. It is a small oligotrichous species characterized by a total length of approximately 21–25 mm, pale yellow to light brown coloration with darker reddish-brown pedipalps, pectinal tooth count of 8 in the male and 7 in the females, Pv = 7–8, Pe-et = 5–6, and a distinct mitochondrial lineage. Phylogenetic analyses based on COI recovered the Rhodian specimens as a strongly supported monophyletic lineage, sister to...

GLP-1 receptor agonist properties of a chimeric peptide derived by hybridization of Latrodectus αLatrotoxin and Heloderma Exendin-4

 


GLP-1 receptor agonist properties of a chimeric peptide derived by hybridization of Latrodectus αLatrotoxin and Heloderma Exendin-4

Abstract

Chimeric peptides comprised of amino acid sequence motifs found within hormones, neuropeptides, and insect or lizard toxins are now under investigation for their potential use in therapeutics. Here, we report the discovery of one such peptide designated as Black Widow Spider-Exendin-4 (BW-Ex-4). It consists of a putative G protein-coupled receptor (GPCR) binding domain present within αLatrotoxin (αLTX) isolated from Latrodectus, and fused to N- and C- terminal motifs found within the glucagon-like peptide-1 receptor (GLP-1R) agonist Exendin-4 isolated from Heloderma. FRET reporter assays that monitor cAMP production establish BW-Ex-4 to be a specific GLP-1R agonist without any stimulatory action at glucose-dependent insulinotropic peptide (GIP), glucagon, or corticotropin releasing hormone (CRH) receptors. Structural modeling studies of the predicted BW-Ex-4 binding sites at GPCRs of Family B provide new insights concerning the molecular basis for chimeric peptide stimulatory actions at the GLP-1R. We also report that BW-Ex-4 acts in obese hyperglycemic Leprdb/db mice to suppress appetite, lower body weight, improve glucoregulation, and to reduce circulating levels of pro-inflammatory cytokines. Collectively, these findings establish combinatorial chimeric peptide chemistry in which αLTX serves as a molecular scaffold for the design of hybrid peptides with novel GPCR stimulating properties.
Chepurny, O. G., Liles, A. N., Cham, N., Matsoukas, M., Liapakis, G., Meng, Q., Cooney, R. N., Doyle, R. P., & Holz, G. G. (2025). GLP-1 receptor agonist properties of a chimeric peptide derived by hybridization of Latrodectus αLatrotoxin and Heloderma Exendin-4. General and Comparative Endocrinology, 114745. https://doi.org/10.1016/j.ygcen.2025.114745