CONFORMATIONAL AND RECEPTOR-BINDING PROPERTIES OF THE INSECT NEUROPEPTIDE PROCTOLIN AND ITS ANALOGS

Proctolin (Arg-Tyr-Leu-Pro-Thr) was the first insect neuropeptide to b e chemically characterised. It plays an essential role in insect neuro physiology and is involved in muscular contraction and neuromodulation . Elements of secondary structure in solution have been studied by com paring data obtained from NMR and molecular dynamics simulations. Diff erent secondary structural requirements are associated with agonist an d antagonist activities. A favoured conformation of proctolin has an i nverse gamma-turn, comprising an intramolecular hydrogen bond near the C-terminal end between Thr NH and Leu CO. Antagonists have a more com pact structure resembling a 'paperclip' loop, containing an intramolec ular hydrogen bond between Tyr NH and Pro CO, possibly stabilised by a salt bridge between the N- and C-terminal groups. A cyclic analogue r etains antagonist activity and resembles a P-bulge loop, also comprisi ng intramolecular hydrogen bonds between Tyr NH and Pro CO and Thr CO. These models may offer feasible starting points for designing novel c ompounds with proctolinergic activity.