Structure–activity relationship of adipokinetic hormone analogs in the striped hawk moth, Hippotion eson

Characterization and pharmacological analysis of two adipokinetic hormone receptor variants of the tsetse fly, Glossina morsitans morsitans

“…In vivo studies in Hippotion eson also showed that its AKHR does not have a preference for either serine or proline at position six (Marco and G€ ade, 2015). The bio-analogues Locmi-AKH-II, Pyrap-AKH, Schgr-AKH-II, Manse-AKH and Hipes-AKH-II were not able to evoke robust Ca 2þ responses when administered to the GlomoAKHRs.…”

“…Substitutions that interrupt the N-terminal amphiphilic pattern of AKH peptides may thereby prevent the formation of the b-strand (Caers et al, 2012;G€ ade and Hayes, 1995;Marco and G€ ade, 2015;Mugumbate et al, 2013). The importance of a phenylalanine residue at position four lies in the fact that it interacts with hydrophobic residues at the N-terminus of the AKHR (Mugumbate et al, 2013).…”

Five Neuropeptide Ligands Meet One Receptor: How Does This Tally? A Structure-Activity Relationship Study Using Adipokinetic Bioassays With the Sphingid Moth, Hippotion eson

“…five, in its corpus cardiacum: two octa- (Hipes-AKH-I and II), two nona- (Hipes-AKH-III and Manse-AKH), and one decapeptide (Manse-AKH-II), which are all active in lipid mobilization (1). (ii) Lacol-AKH from a noctuid moth showed maximal AKH activity in H. eson despite sequence differences and analogs based on Lacol-AKH with modifications at positions 2, 3, 8, or at the termini, as well as C-terminally shortened analogs had reduced or no activity (2). Here we report on N-terminally shortened and modified analogs of the lead peptide, as well as single amino acid substitutions at positions 1, 4, 5, 6, and 7 by an alanine residue.…”

Insight into mosquito GnRH-related neuropeptide receptor specificity revealed through analysis of naturally occurring and synthetic analogs of this neuropeptide family

“…In light of the high fidelity of the three GnRH-related systems (Hansen et al, 2010; Oryan et al, 2018; Wahedi and Paluzzi, 2018), the current study set out to examine for the first time the ligand structure-activity relationship for an insect ACP receptor. This is of utmost importance in order to gain insight on the specific structural features of the ACP system given that extensive studies have been carried out previously on AKH receptors in a variety of species using natural and synthetic analogs of this neuropeptide family (Caers et al, 2012; Fox and Reynolds, 1991; Gäde et al, 2000; Gäde, 1992; Gäde, 1993; Gäde et al, 2016; Keeley et al, 1991; Lee and Goldsworthy, 1996; Lee et al, 1996; Lee et al, 1997; Marco and Gäde, 2015; Marco and Gäde, 2019b; Poulos et al, 1994; Velentza et al, 2000; Ziegler et al, 1991; Ziegler et al, 1998). By examining the activity of a variety of ACP analogs on the activation of the A. aegytpi ACP receptor (ACPR), including single alanine substitutions along with truncated or extended analogs, a few observations can be highlighted.…”

“…Observations correlating with these findings have been made in various studies utilizing in vitro heterologous assays as well as in vivo bioassays monitoring lipid- and/or carbohydrate-mobilizing actions of AKH analogs. Specifically, removal or replacement of the critical aromatics that are archetypal features of AKH neuropeptides found in positions four and eight demonstrates the absolute requirement of these features for receptor activation in heterologous systems or in vivo biological activity (Gäde, 1992; Gäde, 1993; Marco and Gäde, 2015; Marco and Gäde, 2019b).…”