[Frontiers in Bioscience E2, 195-203, January 1, 2010]

A novel dihydroimidazoline, trans-Pro mimetic analog is a selective PK/PBAN agonist

Ronald J. Nachman1, Orna Ben Aziz2, Michael Davidovitch2, Krzysztof Kaczmarek1,3, Janusz Zabrocki1,3, Howard Williams4, Allison Strey1, Miriam Altstein2

1Areawide Pest Management Research, Southern Plains Agricultural Research Center, U.S. Department of Agriculture, College Station, TX 77845, USA, 2Department of Entomology, The Volcani Center, Bet Dagan 50250, Israel, 3Institute of Organic Chemistry, Technical University of Lodz, 90-924 Lodz, Poland, 4Department of Chemistry, Texas A&M University, College Station, TX 77843, USA

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Materials and methods
3.1. Insects
3.2. Peptide and pseudopeptide analog synthesis and purification
3.2.1. Synthesis of PBAN 1-33NH2 , PT, LPK, MT and YFTPRLa
3.2.2. PPK-Jo analog synthesis and purification
3.3. Pheromonotropic bioassay
3.4. Melanotropic bioassay
3.5. Pupariation bioassay
3.6. Myotropic bioassay
3.7. Statistical analysis
3.8. Molecular modeling
4. Results
4.1. Pheromonotropic bioassay
4.2. Melanotropic bioassay
4.3. Pupariation and myotropic bioassays
5. Discussion
6. Acknowledgements
7. References

1. ABSTRACT

The pyrokinin/pheromone biosynthesis activating neuropeptide (PK/PBAN) family plays a significant role in the regulation of reproductive and developmental processes in a variety of insects. A transPro, type I beta-turn has been previously identified as important for the activity of PK/PBAN peptides. A PK/PBAN analog (PPK-Jo) incorporating a novel dihydroimidazole transPro mimetic motif was evaluated in four PK/PBAN bioassays (pheromonotropic, melanotropic, pupariation and hindgut myotropic). PPK-Jo proved to be a pure, selective melanotropic agonist in S. littoralis. The melanotropic receptor in S. littoralis demonstrates more tolerance to deviations from the ideal transPro structure than those of other PK/PBAN assays. The selective PK/PBAN agonist represents a new tool to better understand the endogenous mechanisms of these peptides and serves as a probe of the plasticity of PK/PBAN regulated systems and receptors. The dihydroimidazoline moiety is shown to function as a surrogate for a transPro in certain circumstances, and provides a novel scaffold with which to construct mimetic PK/PBAN analogs with enhanced selectivity and the potential to disrupt critical physiological processes in insect pests.