Hydrogen Bonding Drives Helical Chirality via 10-Membered Rings in Dipeptide Conjugates of Ferrocene-1,1′-Diamine
Considering the enormous importance of protein turns as participants in various biological events, such as protein–protein interactions, great efforts have been made to develop their conformationally and proteolytically stable mimetics. Ferrocene-1,1′-diamine was previously shown to nucleate the sta...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-10-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/20/12233 |
| Summary: | Considering the enormous importance of protein turns as participants in various biological events, such as protein–protein interactions, great efforts have been made to develop their conformationally and proteolytically stable mimetics. Ferrocene-1,1′-diamine was previously shown to nucleate the stable turn structures in peptides prepared by conjugation with Ala (<b>III</b>) and Ala–Pro (<b>VI</b>). Here, we prepared the homochiral conjugates of ferrocene-1,1′-diamine with <span style="font-variant: small-caps;">l</span>-/<span style="font-variant: small-caps;">d</span>-Phe (<b>32/35</b>), <span style="font-variant: small-caps;">l</span>-/<span style="font-variant: small-caps;">d</span>-Val (<b>33/36</b>), and <span style="font-variant: small-caps;">l</span>-/<span style="font-variant: small-caps;">d</span>-Leu (<b>34/37</b>) to investigate (1) whether the organometallic template induces the turn structure upon conjugation with amino acids, and (2) whether the bulky or branched side chains of Phe, Val, and Leu affect hydrogen bonding. Detailed spectroscopic (IR, NMR, CD), X-ray, and DFT studies revealed the presence of two simultaneous 10-membered interstrand hydrogen bonds, i.e., two simultaneous β-turns in goal compounds. A preliminary biological evaluation of <span style="font-variant: small-caps;">d</span>-Leu conjugate <b>37</b> showed its modest potential to induce cell cycle arrest in the G0/G1 phase in the HeLa cell line but these results need further investigation. |
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| ISSN: | 1661-6596 1422-0067 |