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...
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| Format: | Article |
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MDPI AG
2022-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/20/12233 |
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| author | Monika Kovačević Dora Markulin Matea Zelenika Marko Marjanović Marija Lovrić Denis Polančec Marina Ivančić Jasna Mrvčić Krešimir Molčanov Valentina Milašinović Sunčica Roca Ivan Kodrin Lidija Barišić |
| author_facet | Monika Kovačević Dora Markulin Matea Zelenika Marko Marjanović Marija Lovrić Denis Polančec Marina Ivančić Jasna Mrvčić Krešimir Molčanov Valentina Milašinović Sunčica Roca Ivan Kodrin Lidija Barišić |
| author_sort | Monika Kovačević |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T20:06:41Z |
| format | Article |
| id | doaj.art-5cda52b3a55f480eb3bf0a04609b5466 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T20:06:41Z |
| publishDate | 2022-10-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-5cda52b3a55f480eb3bf0a04609b54662023-11-24T00:29:42ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-10-0123201223310.3390/ijms232012233Hydrogen Bonding Drives Helical Chirality via 10-Membered Rings in Dipeptide Conjugates of Ferrocene-1,1′-DiamineMonika Kovačević0Dora Markulin1Matea Zelenika2Marko Marjanović3Marija Lovrić4Denis Polančec5Marina Ivančić6Jasna Mrvčić7Krešimir Molčanov8Valentina Milašinović9Sunčica Roca10Ivan Kodrin11Lidija Barišić12Department of Chemistry and Biochemistry, Faculty of Food Technology and Biotechnology, University of Zagreb, 10000 Zagreb, CroatiaCentral Laboratory, BICRO BIOCENTRE, Ltd., 10000 Zagreb, CroatiaCentral Laboratory, BICRO BIOCENTRE, Ltd., 10000 Zagreb, CroatiaCentral Laboratory, BICRO BIOCENTRE, Ltd., 10000 Zagreb, CroatiaCentral Laboratory, BICRO BIOCENTRE, Ltd., 10000 Zagreb, CroatiaCytomEx, Prisavlje 8, 10000 Zagreb, CroatiaDepartment of Chemistry and Biochemistry, Faculty of Food Technology and Biotechnology, University of Zagreb, 10000 Zagreb, CroatiaDepartment of Food Engineering, Faculty of Food Technology and Biotechnology, University of Zagreb, 10000 Zagreb, CroatiaDivision of Physical Chemistry, Ruđer Bošković Institute, 10000 Zagreb, CroatiaDivision of Physical Chemistry, Ruđer Bošković Institute, 10000 Zagreb, CroatiaNMR Centre, Ruđer Bošković Institute, 10000 Zagreb, CroatiaDepartment of Chemistry, Faculty of Science, University of Zagreb, 10000 Zagreb, CroatiaDepartment of Chemistry and Biochemistry, Faculty of Food Technology and Biotechnology, University of Zagreb, 10000 Zagreb, CroatiaConsidering 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.https://www.mdpi.com/1422-0067/23/20/12233biological activitychiralityconformational analysisDensity Functional Theory (DFT)ferrocenehydrogen bonds |
| spellingShingle | Monika Kovačević Dora Markulin Matea Zelenika Marko Marjanović Marija Lovrić Denis Polančec Marina Ivančić Jasna Mrvčić Krešimir Molčanov Valentina Milašinović Sunčica Roca Ivan Kodrin Lidija Barišić Hydrogen Bonding Drives Helical Chirality via 10-Membered Rings in Dipeptide Conjugates of Ferrocene-1,1′-Diamine International Journal of Molecular Sciences biological activity chirality conformational analysis Density Functional Theory (DFT) ferrocene hydrogen bonds |
| title | Hydrogen Bonding Drives Helical Chirality via 10-Membered Rings in Dipeptide Conjugates of Ferrocene-1,1′-Diamine |
| title_full | Hydrogen Bonding Drives Helical Chirality via 10-Membered Rings in Dipeptide Conjugates of Ferrocene-1,1′-Diamine |
| title_fullStr | Hydrogen Bonding Drives Helical Chirality via 10-Membered Rings in Dipeptide Conjugates of Ferrocene-1,1′-Diamine |
| title_full_unstemmed | Hydrogen Bonding Drives Helical Chirality via 10-Membered Rings in Dipeptide Conjugates of Ferrocene-1,1′-Diamine |
| title_short | Hydrogen Bonding Drives Helical Chirality via 10-Membered Rings in Dipeptide Conjugates of Ferrocene-1,1′-Diamine |
| title_sort | hydrogen bonding drives helical chirality via 10 membered rings in dipeptide conjugates of ferrocene 1 1 diamine |
| topic | biological activity chirality conformational analysis Density Functional Theory (DFT) ferrocene hydrogen bonds |
| url | https://www.mdpi.com/1422-0067/23/20/12233 |
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