New 4-Aminoproline-Based Small Molecule Cyclopeptidomimetics as Potential Modulators of α4β1 Integrin
| Autor: | Irene Casamassima, Franca Zanardi, Elisabetta Portioli, Monica Baiula, Francesca Bianchini, Lucia Battistini, Andrea Sartori, Kelly Bugatti, Agostino Bruno, Claudio Curti |
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| Přispěvatelé: | Sartori A., Bugatti K., Portioli E., Baiula M., Casamassima I., Bruno A., Bianchini F., Curti C., Zanardi F., Battistini L. |
| Rok vydání: | 2021 |
| Předmět: |
Models
Molecular Agonist Proline Molecular model Peptidomimetic Protein Conformation medicine.drug_class Integrin Pharmaceutical Science Jurkat Cell Ligand Aminoproline scaffold Integrin alpha4beta1 Ligands Peptides Cyclic Jurkat cells Article Ligand design Analytical Chemistry Jurkat Cells QD241-441 Drug Discovery Cell Adhesion medicine Humans Physical and Theoretical Chemistry Integrin targeting biology Chemistry Organic Chemistry Adhesion leukocyte integrins Small molecule Biochemistry Chemistry (miscellaneous) peptidomimetic synthesis Leukocyte integrin biology.protein Oligopeptide Molecular Medicine Peptidomimetics Peptidomimetic synthesi Oligopeptides Function (biology) Human Protein Binding |
| Zdroj: | Molecules, Vol 26, Iss 6066, p 6066 (2021) Molecules Volume 26 Issue 19 |
| ISSN: | 1420-3049 |
| DOI: | 10.3390/molecules26196066 |
| Popis: | Integrin α4β1 belongs to the leukocyte integrin family and represents a therapeutic target of relevant interest given its primary role in mediating inflammation, autoimmune pathologies and cancer-related diseases. The focus of the present work is the design, synthesis and characterization of new peptidomimetic compounds that are potentially able to recognize α4β1 integrin and interfere with its function. To this aim, a collection of seven new cyclic peptidomimetics possessing both a 4-aminoproline (Amp) core scaffold grafted onto key α4β1-recognizing sequences and the (2-methylphenyl)ureido-phenylacetyl (MPUPA) appendage, was designed, with the support of molecular modeling studies. The new compounds were synthesized through SPPS procedures followed by in-solution cyclization maneuvers. The biological evaluation of the new cyclic ligands in cell adhesion assays on Jurkat cells revealed promising submicromolar agonist activity in one compound, namely, the c[Amp(MPUPA)Val-Asp-Leu] cyclopeptide. Further investigations will be necessary to complete the characterization of this class of compounds. |
| Databáze: | OpenAIRE |
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