Design of α/β-Hybrid Peptide Ligands of α4β1 Integrin Equipped with a Linkable Side Chain for Chemoselective Biofunctionalization of Microstructured Materials
Arg-Gly-Asp (RGD)-binding integrins, e.g., αvβ3, αvβ1, αvβ5 integrins, are currently regarded as privileged targets for the delivery of diagnostic and theranostic agents, especially in cancer treatment. In contrast, scarce attention has been paid so far to the diagnostic opportunities promised by in...
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| Format: | Article |
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MDPI AG
2021-11-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/9/11/1737 |
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| author | Michele Anselmi Monica Baiula Federica Santino Junwei Zhao Santi Spampinato Natalia Calonghi Luca Gentilucci |
| author_facet | Michele Anselmi Monica Baiula Federica Santino Junwei Zhao Santi Spampinato Natalia Calonghi Luca Gentilucci |
| author_sort | Michele Anselmi |
| collection | DOAJ |
| description | Arg-Gly-Asp (RGD)-binding integrins, e.g., αvβ3, αvβ1, αvβ5 integrins, are currently regarded as privileged targets for the delivery of diagnostic and theranostic agents, especially in cancer treatment. In contrast, scarce attention has been paid so far to the diagnostic opportunities promised by integrins that recognize other peptide motifs. In particular, α4β1 integrin is involved in inflammatory, allergic, and autoimmune diseases, therefore, it represents an interesting therapeutic target. Aiming at obtaining simple, highly stable ligands of α4β1 integrin, we designed hybrid α/β peptidomimetics carrying linkable side chains for the expedient functionalization of biomaterials, nano- and microparticles. We identified the prototypic ligands MPUPA-(<i>R</i>)-isoAsp(NHPr)-Gly-OH (<b>12</b>) and MPUPA-Dap(Ac)-Gly-OH (<b>13</b>) (MPUPA, methylphenylureaphenylacetic acid; Dap, 2,3-diamino propionic acid). Modification of <b>12</b> and <b>13</b> by introduction of flexible linkers at isoAsp or Dap gave <b>49</b> and <b>50</b>, respectively, which allowed for coating with monolayers (ML) of flat zeolite crystals. The resulting peptide–zeolite MLs were able to capture selectively α4β1 integrin-expressing cells. In perspective, the α4β1 integrin ligands identified in this study can find applications for preparing biofunctionalized surfaces and diagnostic devices to control the progression of α4β1 integrin-correlated diseases. |
| first_indexed | 2024-03-10T05:41:50Z |
| format | Article |
| id | doaj.art-faf7fdc793aa4313b46478b618b4081c |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T05:41:50Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-faf7fdc793aa4313b46478b618b4081c2023-11-22T22:32:41ZengMDPI AGBiomedicines2227-90592021-11-01911173710.3390/biomedicines9111737Design of α/β-Hybrid Peptide Ligands of α4β1 Integrin Equipped with a Linkable Side Chain for Chemoselective Biofunctionalization of Microstructured MaterialsMichele Anselmi0Monica Baiula1Federica Santino2Junwei Zhao3Santi Spampinato4Natalia Calonghi5Luca Gentilucci6Department of Chemistry “G. Ciamician”, University of Bologna, Via Selmi 2, 40126 Bologna, ItalyDepartment of Pharmacy and Biotechnology, University of Bologna, Via Irnerio 48, 40126 Bologna, ItalyDepartment of Chemistry “G. Ciamician”, University of Bologna, Via Selmi 2, 40126 Bologna, ItalyDepartment of Chemistry “G. Ciamician”, University of Bologna, Via Selmi 2, 40126 Bologna, ItalyDepartment of Pharmacy and Biotechnology, University of Bologna, Via Irnerio 48, 40126 Bologna, ItalyDepartment of Pharmacy and Biotechnology, University of Bologna, Via Irnerio 48, 40126 Bologna, ItalyDepartment of Chemistry “G. Ciamician”, University of Bologna, Via Selmi 2, 40126 Bologna, ItalyArg-Gly-Asp (RGD)-binding integrins, e.g., αvβ3, αvβ1, αvβ5 integrins, are currently regarded as privileged targets for the delivery of diagnostic and theranostic agents, especially in cancer treatment. In contrast, scarce attention has been paid so far to the diagnostic opportunities promised by integrins that recognize other peptide motifs. In particular, α4β1 integrin is involved in inflammatory, allergic, and autoimmune diseases, therefore, it represents an interesting therapeutic target. Aiming at obtaining simple, highly stable ligands of α4β1 integrin, we designed hybrid α/β peptidomimetics carrying linkable side chains for the expedient functionalization of biomaterials, nano- and microparticles. We identified the prototypic ligands MPUPA-(<i>R</i>)-isoAsp(NHPr)-Gly-OH (<b>12</b>) and MPUPA-Dap(Ac)-Gly-OH (<b>13</b>) (MPUPA, methylphenylureaphenylacetic acid; Dap, 2,3-diamino propionic acid). Modification of <b>12</b> and <b>13</b> by introduction of flexible linkers at isoAsp or Dap gave <b>49</b> and <b>50</b>, respectively, which allowed for coating with monolayers (ML) of flat zeolite crystals. The resulting peptide–zeolite MLs were able to capture selectively α4β1 integrin-expressing cells. In perspective, the α4β1 integrin ligands identified in this study can find applications for preparing biofunctionalized surfaces and diagnostic devices to control the progression of α4β1 integrin-correlated diseases.https://www.mdpi.com/2227-9059/9/11/1737inflammationallergyα4β1 integrinhybrid α/β peptidemonolayerzeolite |
| spellingShingle | Michele Anselmi Monica Baiula Federica Santino Junwei Zhao Santi Spampinato Natalia Calonghi Luca Gentilucci Design of α/β-Hybrid Peptide Ligands of α4β1 Integrin Equipped with a Linkable Side Chain for Chemoselective Biofunctionalization of Microstructured Materials Biomedicines inflammation allergy α4β1 integrin hybrid α/β peptide monolayer zeolite |
| title | Design of α/β-Hybrid Peptide Ligands of α4β1 Integrin Equipped with a Linkable Side Chain for Chemoselective Biofunctionalization of Microstructured Materials |
| title_full | Design of α/β-Hybrid Peptide Ligands of α4β1 Integrin Equipped with a Linkable Side Chain for Chemoselective Biofunctionalization of Microstructured Materials |
| title_fullStr | Design of α/β-Hybrid Peptide Ligands of α4β1 Integrin Equipped with a Linkable Side Chain for Chemoselective Biofunctionalization of Microstructured Materials |
| title_full_unstemmed | Design of α/β-Hybrid Peptide Ligands of α4β1 Integrin Equipped with a Linkable Side Chain for Chemoselective Biofunctionalization of Microstructured Materials |
| title_short | Design of α/β-Hybrid Peptide Ligands of α4β1 Integrin Equipped with a Linkable Side Chain for Chemoselective Biofunctionalization of Microstructured Materials |
| title_sort | design of α β hybrid peptide ligands of α4β1 integrin equipped with a linkable side chain for chemoselective biofunctionalization of microstructured materials |
| topic | inflammation allergy α4β1 integrin hybrid α/β peptide monolayer zeolite |
| url | https://www.mdpi.com/2227-9059/9/11/1737 |
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