Secondary structure determination of insect neuropeptides using high-resolution nuclear magnetic resonance and various molecular mechanics calculations

Insect neuropeptides play a vital role in the hormone release processes associated with insect flight Elucidation of the metabolic flight pathways requires a knowledge of the peptide secondary structure to allow predictions to be made regarding hormone-receptor binding processes. The three insect neuropeptides under investigation were taken from the corpora cardiaca of the migratory locust (Locusta migratoria) and belonged to the Lom peptide series - Lom-AKH-I, II and Ill. The secondary structure of these hormones was investigated using high-resolution nuclear magnetic resonance (NMR) techniques and various molecular mechanics computations. The interproton distances and φ torsion angles obtained from the NMR data were used to constrain the peptides in subsequent Monte Carlo and molecular dynamics (simulated annealing) calculations. The results of these calculations indicated that Lom-AKH-I and Lom-AKH-III adopt a definite structure in d⁶-DMSO solution, while Lom-AKH-II appeared to be fluctional with a minimum of three structures being required to satisfy the experimental data. Lom-AKH-I and ill were shown to adopt a loose open turn structures stabilised by the presence of a single hydrogen bond. Both had an additional concave structure with hydrophobic clustering on the convex surface of the molecule. The results suggest that Lom-AKH-I and Lom-AKH-III are more reactive than Lom-AKH-II. These predictions are in agreement with literature results obtained for Lom-AKH-I and II for lipid mobilisation and phosphorylase activation. However, when measured against cAMP production, Lom-AKH-II has higher activity. Insufficient literature was available to make structure/activity comparisons for Lom-AKH-III.

Grantor dc:publisher.institution

Department of Chemistry

Year dc:date.issued

1996

Author dc:creator

• Sunter, Katherine Margaret

Advisor dc:contributor.advisor

• Jackson, Graham Ellis

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/11427/17558

OAI identifier oai:identifier

oai:open.uct.ac.za:11427/17558