Methodologies for Backbone Macrocyclic Peptide Synthesis Compatible With Screening Technologies
Backbone macrocyclic structures are often found in diverse bioactive peptides and contribute to greater conformational rigidity, peptidase resistance, and potential membrane permeability compared to their linear counterparts. Therefore, such peptide scaffolds are an attractive platform for drug-disc...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-06-01
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| Series: | Frontiers in Chemistry |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fchem.2020.00447/full |
| _version_ | 1818114025216540672 |
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| author | Koki Shinbara Wenyu Liu Renier Herman Pieter van Neer Takayuki Katoh Hiroaki Suga |
| author_facet | Koki Shinbara Wenyu Liu Renier Herman Pieter van Neer Takayuki Katoh Hiroaki Suga |
| author_sort | Koki Shinbara |
| collection | DOAJ |
| description | Backbone macrocyclic structures are often found in diverse bioactive peptides and contribute to greater conformational rigidity, peptidase resistance, and potential membrane permeability compared to their linear counterparts. Therefore, such peptide scaffolds are an attractive platform for drug-discovery endeavors. Recent advances in synthetic methods for backbone macrocyclic peptides have enabled the discovery of novel peptide drug candidates against diverse targets. Here, we overview recent technical advancements in the synthetic methods including 1) enzymatic synthesis, 2) chemical synthesis, 3) split-intein circular ligation of peptides and proteins (SICLOPPS), and 4) in vitro translation system combined with genetic code reprogramming. We also discuss screening methodologies compatible with those synthetic methodologies, such as one-beads one-compound (OBOC) screening compatible with the synthetic method 2, cell-based assay compatible with 3, limiting-dilution PCR and mRNA display compatible with 4. |
| first_indexed | 2024-12-11T03:44:10Z |
| format | Article |
| id | doaj.art-66e75635d61f4aa89128c4cd9f5d487d |
| institution | Directory Open Access Journal |
| issn | 2296-2646 |
| language | English |
| last_indexed | 2024-12-11T03:44:10Z |
| publishDate | 2020-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Chemistry |
| spelling | doaj.art-66e75635d61f4aa89128c4cd9f5d487d2022-12-22T01:22:04ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462020-06-01810.3389/fchem.2020.00447540010Methodologies for Backbone Macrocyclic Peptide Synthesis Compatible With Screening TechnologiesKoki ShinbaraWenyu LiuRenier Herman Pieter van NeerTakayuki KatohHiroaki SugaBackbone macrocyclic structures are often found in diverse bioactive peptides and contribute to greater conformational rigidity, peptidase resistance, and potential membrane permeability compared to their linear counterparts. Therefore, such peptide scaffolds are an attractive platform for drug-discovery endeavors. Recent advances in synthetic methods for backbone macrocyclic peptides have enabled the discovery of novel peptide drug candidates against diverse targets. Here, we overview recent technical advancements in the synthetic methods including 1) enzymatic synthesis, 2) chemical synthesis, 3) split-intein circular ligation of peptides and proteins (SICLOPPS), and 4) in vitro translation system combined with genetic code reprogramming. We also discuss screening methodologies compatible with those synthetic methodologies, such as one-beads one-compound (OBOC) screening compatible with the synthetic method 2, cell-based assay compatible with 3, limiting-dilution PCR and mRNA display compatible with 4.https://www.frontiersin.org/article/10.3389/fchem.2020.00447/fullnon-proteinogenic amino acidbackbone macrocyclic peptideenzymatic peptide backbone cyclizationpeptide libraryOBOC screeningSICLOPPS |
| spellingShingle | Koki Shinbara Wenyu Liu Renier Herman Pieter van Neer Takayuki Katoh Hiroaki Suga Methodologies for Backbone Macrocyclic Peptide Synthesis Compatible With Screening Technologies Frontiers in Chemistry non-proteinogenic amino acid backbone macrocyclic peptide enzymatic peptide backbone cyclization peptide library OBOC screening SICLOPPS |
| title | Methodologies for Backbone Macrocyclic Peptide Synthesis Compatible With Screening Technologies |
| title_full | Methodologies for Backbone Macrocyclic Peptide Synthesis Compatible With Screening Technologies |
| title_fullStr | Methodologies for Backbone Macrocyclic Peptide Synthesis Compatible With Screening Technologies |
| title_full_unstemmed | Methodologies for Backbone Macrocyclic Peptide Synthesis Compatible With Screening Technologies |
| title_short | Methodologies for Backbone Macrocyclic Peptide Synthesis Compatible With Screening Technologies |
| title_sort | methodologies for backbone macrocyclic peptide synthesis compatible with screening technologies |
| topic | non-proteinogenic amino acid backbone macrocyclic peptide enzymatic peptide backbone cyclization peptide library OBOC screening SICLOPPS |
| url | https://www.frontiersin.org/article/10.3389/fchem.2020.00447/full |
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