New proctolin analogues modified by d-amino acids in the peptide chain and their high cardioexcitatory effect on Tenebrio molitor

The object of our studies was the synthesis and conformational and biological evaluation of the series of 14 analogues of the insect neuropeptide, proctolin. The analogues were obtained by replacement of the native l‐amino acids by their d‐isomers in one, two, and all positions. Biological effects of the peptides were examined by cardioexcitatory test on the heart of yellow mealworm, Tenebrio molitor, in vitro. In biotest performed on insects, d‐Arg‐d‐Tyr‐d‐Leu‐d‐Pro‐d‐Thr. [d‐Arg(N‐G‐nitro)1,d‐Leu3]‐, [d‐Argl,d‐Leu3]‐, [d‐Tyr2,d‐Thr5]‐ and [d‐Arg1,d‐Pro4]‐proctolin exert high agonistic activity of proctolin on the heart of insects at 10−11‐10−10 M concentrations. The proctolin analogue containing only d‐amino acid residues in the peptide chain unexpectedly shows a much higher cardioexcitatory effect than the native peptide. Moreover, preliminary CD and NMR conformational studies show that proctolin analogues investigated here seem to prefer rather ordered structures. although their conformations differ in some cases. © Munksgaard 1996.