About this Research Topic
Integrins are one of most important families of cell adhesion receptors that mediate cell-cell and cell-extracellular matrix interactions. All integrins are heterodimeric transmembrane proteins made up of stable non-covalent associations between α and β subunits. In mammals, only 24 different combinations have been identified combining 18 α subunits and 8 β subunits. Integrins are involved in tissue integrity and cell trafficking, growth, differentiation, proliferation, migration, and in signal transduction. Integrins also function in pathological processes such as inflammation, wound healing, angiogenesis, and tumor metastasis. Therefore, pharmacological inhibition of integrin is of great interest in the treatment and prevention of disease. The synthesis of antagonists capable of blocking the interaction of integrin with their cell adhesion molecule (CAM) or ECM ligands may represent a novel approach in the treatment of these pathologies.
The aim of this Research Topic is to identify new integrin antagonists and explore recent applications such as bioconjugation with nanoparticles (NPs). Integrin ligands, such as RDG, LDV or BIO1211 show high activity in vitro but rapid enzymatic hydrolysis and clearance in vivo. Mimetics with unnatural amino acids or heterocycles and small molecule moieties have been developed in order to increase the metabolic stability of the ligands. An alternative strategy is head-to-tail cyclization, and all of these approaches are widely used in the preparation of antagonists to block the action of proteolytic enzymes. A major unresolved issue in the development of new integrin antagonists is a low level of activity when compared to the precursor, for example RGD or BIO1211. Conjugation of peptides to NPs represents an effective approach to addressing the intrinsic drawbacks of the peptides, providing access to a variety of biomedical uses. Specifically, this conjugation increases the circulating half-lives of the peptides in vivo, reducing the need for frequent administrations to sustain their efficacy. In general, the development of innovative methods will not only broaden the synthetic chemistry scope of these antagonists, but will also help to identify the structural novel types of antagonist mimetics for all possible applications.
We welcome authors to contribute their Original Research articles, as well as Reviews, to this collection. Potential topics related to integrins include, but are not limited to:
• New methodologies to prepare integrin antagonists
• Synthesis of new ligands
• Bioconjugation on nanoparticles
• Development of the new bonds between ligands and biomaterials
• Novel scaffolds to prepare mimetics of peptide ligands
• Structure-Activity Relationship analysis
• New sustainable methodologies
The aim of this Research Topic is to identify new integrin antagonists and explore recent applications such as bioconjugation with nanoparticles (NPs). Integrin ligands, such as RDG, LDV or BIO1211 show high activity in vitro but rapid enzymatic hydrolysis and clearance in vivo. Mimetics with unnatural amino acids or heterocycles and small molecule moieties have been developed in order to increase the metabolic stability of the ligands. An alternative strategy is head-to-tail cyclization, and all of these approaches are widely used in the preparation of antagonists to block the action of proteolytic enzymes. A major unresolved issue in the development of new integrin antagonists is a low level of activity when compared to the precursor, for example RGD or BIO1211. Conjugation of peptides to NPs represents an effective approach to addressing the intrinsic drawbacks of the peptides, providing access to a variety of biomedical uses. Specifically, this conjugation increases the circulating half-lives of the peptides in vivo, reducing the need for frequent administrations to sustain their efficacy. In general, the development of innovative methods will not only broaden the synthetic chemistry scope of these antagonists, but will also help to identify the structural novel types of antagonist mimetics for all possible applications.
We welcome authors to contribute their Original Research articles, as well as Reviews, to this collection. Potential topics related to integrins include, but are not limited to:
• New methodologies to prepare integrin antagonists
• Synthesis of new ligands
• Bioconjugation on nanoparticles
• Development of the new bonds between ligands and biomaterials
• Novel scaffolds to prepare mimetics of peptide ligands
• Structure-Activity Relationship analysis
• New sustainable methodologies
Keywords: integrin, ligand, SAR, antagonist, peptidomimetics
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
