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. 2021 May 28;26(11):3271.
doi: 10.3390/molecules26113271.

Solid-Phase Synthesis of an Insect Pyrokinin Analog Incorporating an Imidazoline Ring as Isosteric Replacement of a trans Peptide Bond

Krzysztof Kaczmarek  1   2 , Barbara Pacholczyk-Sienicka  2 , Łukasz Albrecht  2 , Janusz Zabrocki  1   2 , Ronald J Nachman  1
Affiliations

Solid-Phase Synthesis of an Insect Pyrokinin Analog Incorporating an Imidazoline Ring as Isosteric Replacement of a trans Peptide Bond

Krzysztof Kaczmarek et al. Molecules. .

Abstract

A facile solid-phase synthetic method for incorporating the imidazoline ring motif, a surrogate for a trans peptide bond, into bioactive peptides is reported. The example described is the synthesis of an imidazoline peptidomimetic analog of an insect pyrokinin neuropeptide via a cyclization reaction of an iminium salt generated from the preceding amino acid and 2,4-diaminopropanoic acid (Dap).

Keywords: SPOS; imidazoline ring; insect neuropeptides; pyrokinins; trans peptide bond.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Comparison between trans peptide bond structure (right) and imidazoline moiety (left) as a peptide bond replacement, and which mimics trans geometry irreversibly.
Figure 2
Figure 2
Structure of PPK-Jo, a selective agonist in one of four PK-related bioassays [3,5].
Figure 3
Figure 3
Synthesis of the iminoether 2 derived from Fmoc-L-Ala-NH2 1, followed by ring formation on solid support: (i) 1.1 eq. triethyloxonium tetrafluoroborate or triethyloxonium hexafluorophosphate in DCM, rt, 2 h; (ii) washing with 1 M KHCO3 aq., overnight drying over anhydrous MgSO4; (iii) DIEA/DCM, rt, overnight; (iv) Boc2O/DIEA, rt, 3 h.
Figure 4
Figure 4
Structure of PPK-Jo with shifts of H (red) and C (blue) atoms displayed.
See this image and copyright information in PMC

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