Comparative Metabolism of α- and β-Peptides in the Insect Heliothis virescens and in Plant Cells of Black Mexican Sweet Maize

The tripeptide H‐Val‐Ala‐Leu‐OH and the N‐Ac‐tetrapeptide amide Ac‐Thr‐Lys‐Trp‐Phe‐NH2, and their β‐peptidic counterparts H‐β3hVal‐β3hAla‐β3hLeu‐OH and Ac‐β3hThr‐(S)β2hLys‐β3hTrp‐β3hPhe‐NH2, respectively, have been injected into Heliothis virescens larvae and added to cell cultures of black mexican sweet maize. The body liquids of the larvae and the supernatant of the plant cell cultures were sampled 0, 2, 3, 6, 17, and/or 24 h after application and analyzed by LC/MS. While the two α‐peptides were degraded rapidly in these environments, the concentration of the β‐peptides was found to decrease very slowly. Thus, ca. 60% of the original amount of the β‐tetrapeptide was detected in the liquids of the insect after 24 h. The plant cells did not seem to make use of the β‐peptides at all, whereas, the α‐tripeptide completely disappeared from the supernatant after 3 h. Thus, we have demonstrated, for the first time, the high stability of β‐peptides against degradation and metabolism in an insect and a plant. Especially remarkable is the persistence of the β‐tetrapeptide with its functionalised and, thus, ‘metabolisable’ side chains of Thr, Lys, Trp, and Phe in the insect larvae, which are known to have a high level of activity of oxidizing enzymes. The results described here match those of ADME investigations with radioactively labeled β‐peptides in rats, where essentially complete stability has been observed, while environmental microorganisms have been found to biodegrade β‐peptides, albeit slowly. Possible implications of these findings for biomedical and pest‐control applications are proposed.