Solid-phase Synthesis of Tetrapeptide on 2-Chlorotrityl Chloride Resin by Using Benzotriazol-1-yl-oxytripyrrolidinophosphonium Hexafluorophosphate as Coupling Reagent
Tetrapeptide, OH-Pro-Ala-Gly-Tyr-NH2, was successfully synthesised on 2-chlorotrityl chloride resin by taking advantage of PyBOP (benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate) as coupling reagent. The selection of the peptide as the target of synthesis was due to its interestin...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | Indonesian |
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Syarif Hidayatullah Jakarta State Islamic University
2016-12-01
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| Series: | Jurnal Kimia Valensi |
| Subjects: | |
| Online Access: | http://journal.uinjkt.ac.id/index.php/valensi/article/view/4055 |
| _version_ | 1818083631594209280 |
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| author | Rani Maharani Nuruzzahra Ammatillah Gunawan Gunawan Ace Tatang Hidayat |
| author_facet | Rani Maharani Nuruzzahra Ammatillah Gunawan Gunawan Ace Tatang Hidayat |
| author_sort | Rani Maharani |
| collection | DOAJ |
| description | Tetrapeptide, OH-Pro-Ala-Gly-Tyr-NH2, was successfully synthesised on 2-chlorotrityl chloride resin by taking advantage of PyBOP (benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate) as coupling reagent. The selection of the peptide as the target of synthesis was due to its interesting bioactivity as antioxidant. The synthesis was undertaken with Fmoc strategy, where Fmoc-proline was added onto the resin at the first place. It is known from the literature that proline can resist from rasemisation when it was attached on the resin at the first time. Fmoc deprotection step was carried out by employing 20% piperidine in DMF and the reaction mixture was shaken for 30 minutes. Once the proline attached, the next step was to attach amino acids, alanine (Ala), glycine (Gly) and tyrosine(Tyr), subsequently onto the resin until tetrapeptidyl resin was constructed on the resin. Hydroxyl group of Tyr was protected with t-butyl, which is TFA-labiled. Coupling reaction was undertaken by mixing the amino acid and PyBOP in a mixture of dichloromethane and DMF (1:1) and in the presence of basic DIPEA. Resin cleavage step was carried out by using 95% TFA in water, where t-butyl protecting group on the side chain of Tyr was cleaved at the same time. The analytical RP-HPLC of the final product showed a single peak at 21.9 minutes (20-90% of acetonitrile in water with 0.1% of TFA during 30 minutes), indicating that each coupling has given a good coupling performance and resulting in a pure product. The desired product showed the correct molecular weight with m/z 407.2 [M+H]+ and 429.2 [M+Na].
DOI: http://dx.doi.org/10.15408/jkv.v0i0.4055 |
| first_indexed | 2024-12-10T19:41:04Z |
| format | Article |
| id | doaj.art-dcf0240737914487aba933832304b2d1 |
| institution | Directory Open Access Journal |
| issn | 2460-6065 2548-3013 |
| language | Indonesian |
| last_indexed | 2024-12-10T19:41:04Z |
| publishDate | 2016-12-01 |
| publisher | Syarif Hidayatullah Jakarta State Islamic University |
| record_format | Article |
| series | Jurnal Kimia Valensi |
| spelling | doaj.art-dcf0240737914487aba933832304b2d12022-12-22T01:35:59ZindSyarif Hidayatullah Jakarta State Islamic UniversityJurnal Kimia Valensi2460-60652548-30132016-12-0122859010.15408/jkv.v2i2.40553183Solid-phase Synthesis of Tetrapeptide on 2-Chlorotrityl Chloride Resin by Using Benzotriazol-1-yl-oxytripyrrolidinophosphonium Hexafluorophosphate as Coupling ReagentRani Maharani0Nuruzzahra Ammatillah1Gunawan Gunawan2Ace Tatang Hidayat3Department of Chemistry, Padjajaran University, Jalan Raya Bandung-Sumedang Km 21 Jatinangor Kabupaten Sumedang 45363 West Java IndonesiaDepartment of Chemistry, Padjajaran University, Jalan Raya Bandung-Sumedang Km 21 Jatinangor Kabupaten Sumedang 45363 West Java IndonesiaDepartment of Chemistry, Padjajaran University, Jalan Raya Bandung-Sumedang Km 21 Jatinangor Kabupaten Sumedang 45363 West Java IndonesiaDepartment of Chemistry, Padjajaran University, Jalan Raya Bandung-Sumedang Km 21 Jatinangor Kabupaten Sumedang 45363 West Java IndonesiaTetrapeptide, OH-Pro-Ala-Gly-Tyr-NH2, was successfully synthesised on 2-chlorotrityl chloride resin by taking advantage of PyBOP (benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate) as coupling reagent. The selection of the peptide as the target of synthesis was due to its interesting bioactivity as antioxidant. The synthesis was undertaken with Fmoc strategy, where Fmoc-proline was added onto the resin at the first place. It is known from the literature that proline can resist from rasemisation when it was attached on the resin at the first time. Fmoc deprotection step was carried out by employing 20% piperidine in DMF and the reaction mixture was shaken for 30 minutes. Once the proline attached, the next step was to attach amino acids, alanine (Ala), glycine (Gly) and tyrosine(Tyr), subsequently onto the resin until tetrapeptidyl resin was constructed on the resin. Hydroxyl group of Tyr was protected with t-butyl, which is TFA-labiled. Coupling reaction was undertaken by mixing the amino acid and PyBOP in a mixture of dichloromethane and DMF (1:1) and in the presence of basic DIPEA. Resin cleavage step was carried out by using 95% TFA in water, where t-butyl protecting group on the side chain of Tyr was cleaved at the same time. The analytical RP-HPLC of the final product showed a single peak at 21.9 minutes (20-90% of acetonitrile in water with 0.1% of TFA during 30 minutes), indicating that each coupling has given a good coupling performance and resulting in a pure product. The desired product showed the correct molecular weight with m/z 407.2 [M+H]+ and 429.2 [M+Na]. DOI: http://dx.doi.org/10.15408/jkv.v0i0.4055http://journal.uinjkt.ac.id/index.php/valensi/article/view/4055solid-phase peptide synthesistetrapeptide2-chlorotrityl chloridepybopfmoc strategy |
| spellingShingle | Rani Maharani Nuruzzahra Ammatillah Gunawan Gunawan Ace Tatang Hidayat Solid-phase Synthesis of Tetrapeptide on 2-Chlorotrityl Chloride Resin by Using Benzotriazol-1-yl-oxytripyrrolidinophosphonium Hexafluorophosphate as Coupling Reagent Jurnal Kimia Valensi solid-phase peptide synthesis tetrapeptide 2-chlorotrityl chloride pybop fmoc strategy |
| title | Solid-phase Synthesis of Tetrapeptide on 2-Chlorotrityl Chloride Resin by Using Benzotriazol-1-yl-oxytripyrrolidinophosphonium Hexafluorophosphate as Coupling Reagent |
| title_full | Solid-phase Synthesis of Tetrapeptide on 2-Chlorotrityl Chloride Resin by Using Benzotriazol-1-yl-oxytripyrrolidinophosphonium Hexafluorophosphate as Coupling Reagent |
| title_fullStr | Solid-phase Synthesis of Tetrapeptide on 2-Chlorotrityl Chloride Resin by Using Benzotriazol-1-yl-oxytripyrrolidinophosphonium Hexafluorophosphate as Coupling Reagent |
| title_full_unstemmed | Solid-phase Synthesis of Tetrapeptide on 2-Chlorotrityl Chloride Resin by Using Benzotriazol-1-yl-oxytripyrrolidinophosphonium Hexafluorophosphate as Coupling Reagent |
| title_short | Solid-phase Synthesis of Tetrapeptide on 2-Chlorotrityl Chloride Resin by Using Benzotriazol-1-yl-oxytripyrrolidinophosphonium Hexafluorophosphate as Coupling Reagent |
| title_sort | solid phase synthesis of tetrapeptide on 2 chlorotrityl chloride resin by using benzotriazol 1 yl oxytripyrrolidinophosphonium hexafluorophosphate as coupling reagent |
| topic | solid-phase peptide synthesis tetrapeptide 2-chlorotrityl chloride pybop fmoc strategy |
| url | http://journal.uinjkt.ac.id/index.php/valensi/article/view/4055 |
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