Synthesis of Novel Arginine Building Blocks with Increased Lipophilicity Compatible with Solid-Phase Peptide Synthesis
Arginine, due to the guanidine moiety, increases peptides’ hydrophilicity and enables interactions with charged molecules, but at the same time, its presence in a peptide chain might reduce its permeability through biological membranes. This might be resolved by temporary coverage of the peptide cha...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-11-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/23/7780 |
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| author | Mladena Glavaš Agata Gitlin-Domagalska Natalia Ptaszyńska Dominika Starego Sylwia Freza Dawid Dębowski Aleksandra Helbik-Maciejewska Anna Łęgowska Chaim Gilon Krzysztof Rolka |
| author_facet | Mladena Glavaš Agata Gitlin-Domagalska Natalia Ptaszyńska Dominika Starego Sylwia Freza Dawid Dębowski Aleksandra Helbik-Maciejewska Anna Łęgowska Chaim Gilon Krzysztof Rolka |
| author_sort | Mladena Glavaš |
| collection | DOAJ |
| description | Arginine, due to the guanidine moiety, increases peptides’ hydrophilicity and enables interactions with charged molecules, but at the same time, its presence in a peptide chain might reduce its permeability through biological membranes. This might be resolved by temporary coverage of the peptide charge by lipophilic, enzyme-sensitive alkoxycarbonyl groups. Unfortunately, such a modification of a guanidine moiety has not been reported to date and turned out to be challenging. Here, we present a new, optimized strategy to obtain arginine building blocks with increased lipophilicity that were successfully utilized in the solid-phase peptide synthesis of novel arginine vasopressin prodrugs. |
| first_indexed | 2024-03-09T01:46:11Z |
| format | Article |
| id | doaj.art-989f5ba2e7a34153ac3dd01b70a7256f |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T01:46:11Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-989f5ba2e7a34153ac3dd01b70a7256f2023-12-08T15:22:19ZengMDPI AGMolecules1420-30492023-11-012823778010.3390/molecules28237780Synthesis of Novel Arginine Building Blocks with Increased Lipophilicity Compatible with Solid-Phase Peptide SynthesisMladena Glavaš0Agata Gitlin-Domagalska1Natalia Ptaszyńska2Dominika Starego3Sylwia Freza4Dawid Dębowski5Aleksandra Helbik-Maciejewska6Anna Łęgowska7Chaim Gilon8Krzysztof Rolka9Department of Molecular Biochemistry, Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-308 Gdansk, PolandDepartment of Molecular Biochemistry, Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-308 Gdansk, PolandDepartment of Molecular Biochemistry, Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-308 Gdansk, PolandDepartment of Molecular Biochemistry, Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-308 Gdansk, PolandDepartment of Theoretical Chemistry, Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-308 Gdansk, PolandDepartment of Molecular Biochemistry, Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-308 Gdansk, PolandDepartment of Molecular Biochemistry, Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-308 Gdansk, PolandDepartment of Molecular Biochemistry, Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-308 Gdansk, PolandDepartment of Organic Chemistry, Institute of Chemistry, The Hebrew University, Jerusalem 91904, IsraelDepartment of Molecular Biochemistry, Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-308 Gdansk, PolandArginine, due to the guanidine moiety, increases peptides’ hydrophilicity and enables interactions with charged molecules, but at the same time, its presence in a peptide chain might reduce its permeability through biological membranes. This might be resolved by temporary coverage of the peptide charge by lipophilic, enzyme-sensitive alkoxycarbonyl groups. Unfortunately, such a modification of a guanidine moiety has not been reported to date and turned out to be challenging. Here, we present a new, optimized strategy to obtain arginine building blocks with increased lipophilicity that were successfully utilized in the solid-phase peptide synthesis of novel arginine vasopressin prodrugs.https://www.mdpi.com/1420-3049/28/23/7780arginine building blocksincreased lipophilicitySPPSvasopressinprodrugs |
| spellingShingle | Mladena Glavaš Agata Gitlin-Domagalska Natalia Ptaszyńska Dominika Starego Sylwia Freza Dawid Dębowski Aleksandra Helbik-Maciejewska Anna Łęgowska Chaim Gilon Krzysztof Rolka Synthesis of Novel Arginine Building Blocks with Increased Lipophilicity Compatible with Solid-Phase Peptide Synthesis Molecules arginine building blocks increased lipophilicity SPPS vasopressin prodrugs |
| title | Synthesis of Novel Arginine Building Blocks with Increased Lipophilicity Compatible with Solid-Phase Peptide Synthesis |
| title_full | Synthesis of Novel Arginine Building Blocks with Increased Lipophilicity Compatible with Solid-Phase Peptide Synthesis |
| title_fullStr | Synthesis of Novel Arginine Building Blocks with Increased Lipophilicity Compatible with Solid-Phase Peptide Synthesis |
| title_full_unstemmed | Synthesis of Novel Arginine Building Blocks with Increased Lipophilicity Compatible with Solid-Phase Peptide Synthesis |
| title_short | Synthesis of Novel Arginine Building Blocks with Increased Lipophilicity Compatible with Solid-Phase Peptide Synthesis |
| title_sort | synthesis of novel arginine building blocks with increased lipophilicity compatible with solid phase peptide synthesis |
| topic | arginine building blocks increased lipophilicity SPPS vasopressin prodrugs |
| url | https://www.mdpi.com/1420-3049/28/23/7780 |
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