Abstract
Insect neuropeptides of the insect kinin class share a common C‐terminal pentapeptide sequence F^1^X~1~^2^X~2~^3^W^4^G^5^‐NH~2~ (X~2~^3^ = P, S, A) and regulate such critical physiological processes as water balance and digestive enzyme release. Analogs of the insect kinin class, in which the critical residues of F^1^, P^3^, and W^4^ were replaced with β^3^‐amino acid or their β^2^‐homo‐amino acid variants, have been synthesized by the solid phase peptide strategy. The resulting single‐ and double‐replacement analogs were evaluated in an insect diuretic assay and enzyme digestion trials. Analogs modified in the core P^3^ position produce a potent and efficacious diuretic response that is not significantly different from that obtained with the endogenous achetakinin peptides. The analogs also demonstrate enhanced resistance to hydrolysis by ACE and NEP, endopeptidases that inactivate the natural insect neuropeptides. This paper describes the first instance of β‐amino acids analogs of an arthropod peptide that demonstrate significant bioactivity and resistance to peptidase degradation. © 2006 Wiley Wiley Periodicals, Inc. Biopolymers (Pept Sci) 88:76–82, 2007.
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