Conformational Preferences and Antiproliferative Activity of Peptidomimetics Containing Methyl 1′-Aminoferrocene-1-carboxylate and Turn-Forming Homo- and Heterochiral Pro-Ala Motifs
The concept of peptidomimetics is based on structural modifications of natural peptides that aim not only to mimic their 3D shape and biological function, but also to reduce their limitations. The peptidomimetic approach is used in medicinal chemistry to develop drug-like compounds that are more act...
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2021-12-01
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| author | Monika Kovačević Mojca Čakić Semenčić Kristina Radošević Krešimir Molčanov Sunčica Roca Lucija Šimunović Ivan Kodrin Lidija Barišić |
| author_facet | Monika Kovačević Mojca Čakić Semenčić Kristina Radošević Krešimir Molčanov Sunčica Roca Lucija Šimunović Ivan Kodrin Lidija Barišić |
| author_sort | Monika Kovačević |
| collection | DOAJ |
| description | The concept of peptidomimetics is based on structural modifications of natural peptides that aim not only to mimic their 3D shape and biological function, but also to reduce their limitations. The peptidomimetic approach is used in medicinal chemistry to develop drug-like compounds that are more active and selective than natural peptides and have fewer side effects. One of the synthetic strategies for obtaining peptidomimetics involves mimicking peptide α-helices, β-sheets or turns. Turns are usually located on the protein surface where they interact with various receptors and are therefore involved in numerous biological events. Among the various synthetic tools for turn mimetic design reported so far, our group uses an approach based on the insertion of different ferrocene templates into the peptide backbone that both induce turn formation and reduce conformational flexibility. Here, we conjugated methyl 1′-aminoferrocene-carboxylate with homo- and heterochiral Pro-Ala dipeptides to investigate the turn formation potential and antiproliferative properties of the resulting peptidomimetics <b>2</b>–<b>5</b>. Detailed spectroscopic (IR, NMR, CD), X-ray and DFT studies showed that the heterochiral conjugates <b>2</b> and <b>3</b> were more suitable for the formation of β-turns. Cell viability study, clonogenic assay and cell death analysis showed the highest biological potential of homochiral peptide <b>4</b>. |
| first_indexed | 2024-03-10T03:55:40Z |
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| id | doaj.art-79a002f5d19f4f74b03b809725a5866d |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T03:55:40Z |
| publishDate | 2021-12-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-79a002f5d19f4f74b03b809725a5866d2023-11-23T08:47:47ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-12-0122241353210.3390/ijms222413532Conformational Preferences and Antiproliferative Activity of Peptidomimetics Containing Methyl 1′-Aminoferrocene-1-carboxylate and Turn-Forming Homo- and Heterochiral Pro-Ala MotifsMonika Kovačević0Mojca Čakić Semenčić1Kristina Radošević2Krešimir Molčanov3Sunčica Roca4Lucija Šimunović5Ivan Kodrin6Lidija Barišić7Department of Chemistry and Biochemistry, Faculty of Food Technology and Biotechnology, University of Zagreb, 10000 Zagreb, CroatiaDepartment of Chemistry and Biochemistry, Faculty of Food Technology and Biotechnology, University of Zagreb, 10000 Zagreb, CroatiaDepartment of Biochemical Engineering, Faculty of Food Technology and Biotechnology, University of Zagreb, 10000 Zagreb, CroatiaDivision of Physical Chemistry, Ruđer Bošković Institute, 10000 Zagreb, CroatiaNMR Centre, Ruđer Bošković Institute, 10000 Zagreb, CroatiaDepartment of Chemistry and Biochemistry, Faculty of Food Technology and Biotechnology, University of Zagreb, 10000 Zagreb, CroatiaDepartment of Organic 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, CroatiaThe concept of peptidomimetics is based on structural modifications of natural peptides that aim not only to mimic their 3D shape and biological function, but also to reduce their limitations. The peptidomimetic approach is used in medicinal chemistry to develop drug-like compounds that are more active and selective than natural peptides and have fewer side effects. One of the synthetic strategies for obtaining peptidomimetics involves mimicking peptide α-helices, β-sheets or turns. Turns are usually located on the protein surface where they interact with various receptors and are therefore involved in numerous biological events. Among the various synthetic tools for turn mimetic design reported so far, our group uses an approach based on the insertion of different ferrocene templates into the peptide backbone that both induce turn formation and reduce conformational flexibility. Here, we conjugated methyl 1′-aminoferrocene-carboxylate with homo- and heterochiral Pro-Ala dipeptides to investigate the turn formation potential and antiproliferative properties of the resulting peptidomimetics <b>2</b>–<b>5</b>. Detailed spectroscopic (IR, NMR, CD), X-ray and DFT studies showed that the heterochiral conjugates <b>2</b> and <b>3</b> were more suitable for the formation of β-turns. Cell viability study, clonogenic assay and cell death analysis showed the highest biological potential of homochiral peptide <b>4</b>.https://www.mdpi.com/1422-0067/22/24/13532antiproliferative activitychiralityconformational analysisdensity functional theory (DFT)ferrocenehydrogen bonds |
| spellingShingle | Monika Kovačević Mojca Čakić Semenčić Kristina Radošević Krešimir Molčanov Sunčica Roca Lucija Šimunović Ivan Kodrin Lidija Barišić Conformational Preferences and Antiproliferative Activity of Peptidomimetics Containing Methyl 1′-Aminoferrocene-1-carboxylate and Turn-Forming Homo- and Heterochiral Pro-Ala Motifs International Journal of Molecular Sciences antiproliferative activity chirality conformational analysis density functional theory (DFT) ferrocene hydrogen bonds |
| title | Conformational Preferences and Antiproliferative Activity of Peptidomimetics Containing Methyl 1′-Aminoferrocene-1-carboxylate and Turn-Forming Homo- and Heterochiral Pro-Ala Motifs |
| title_full | Conformational Preferences and Antiproliferative Activity of Peptidomimetics Containing Methyl 1′-Aminoferrocene-1-carboxylate and Turn-Forming Homo- and Heterochiral Pro-Ala Motifs |
| title_fullStr | Conformational Preferences and Antiproliferative Activity of Peptidomimetics Containing Methyl 1′-Aminoferrocene-1-carboxylate and Turn-Forming Homo- and Heterochiral Pro-Ala Motifs |
| title_full_unstemmed | Conformational Preferences and Antiproliferative Activity of Peptidomimetics Containing Methyl 1′-Aminoferrocene-1-carboxylate and Turn-Forming Homo- and Heterochiral Pro-Ala Motifs |
| title_short | Conformational Preferences and Antiproliferative Activity of Peptidomimetics Containing Methyl 1′-Aminoferrocene-1-carboxylate and Turn-Forming Homo- and Heterochiral Pro-Ala Motifs |
| title_sort | conformational preferences and antiproliferative activity of peptidomimetics containing methyl 1 aminoferrocene 1 carboxylate and turn forming homo and heterochiral pro ala motifs |
| topic | antiproliferative activity chirality conformational analysis density functional theory (DFT) ferrocene hydrogen bonds |
| url | https://www.mdpi.com/1422-0067/22/24/13532 |
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