These findings highlight the role of α integrin in allergic conjunctivitis and suggest that DS-70 is a potential treatment for this condition.

The use of organic dyes to promote organic reactions by photoredox catalysis is continuosly expanding, and was recently reviewed by Nicewicz. The synthesis of new dyes, their application in flow...

Persistent accumulation of immune cells mediated by α4β1 integrin (VLA-4) is a hallmark of the inflammatory diseases and of chronic inflammation observed in the affected tissues of autoimmune diseases. Aiming at exploring new methods for monitoring the course of the inflammatory processes, we designed the first peptide-functionalized nanostructured devices capable to mimic the high-density multivalency binding between the α4β1 integrin-expressing cells and the ligands overexpressed on the endothelial surfaces, in the proximity of the sites of inflammation. Specifically, we describe the first examples of monolayers constituted by dye-loaded zeolite L crystals, coated with α4β1 integrin peptide ligands, and we analyze the adhesion of model Jurkat cells in comparison to non-α4β1 integrin-expressing cells. In particular, the peptidomimetic diphenylurea-Leu-Asp-Val-diamine allows significant and selective detection of α4β1 integrin-expressing Jurkat cells, after very rapid incubation time, supporting the possible implementation in a diagnostic device capable to detect the desired cells from biological fluids, obtainable from patients in a noninvasive way.

α4β1 integrin is a cell adhesion receptor deeply involved in the migration and accumulation of leukocytes. Therefore, integrin antagonists that inhibit leukocytes recruitment are currently regarded as a therapeutic opportunity for the treatment of inflammatory disorder, including leukocyte-related autoimmune diseases. Recently, it has been suggested that integrin agonists capable to prevent the release of adherent leukocytes might serve as therapeutic agents as well. However, very few α4β1 integrin agonists have been discovered so far, thus precluding the investigation of their potential therapeutic efficacy. In this perspective, we synthesized cyclopeptides containing the LDV recognition motif found in the native ligand fibronectin. This approach led to the discovery of potent agonists capable to increase the adhesion of α4 integrin-expressing cells. Conformational and quantum mechanics computations predicted distinct ligand–receptor interactions for antagonists or agonists, plausibly referable to receptor inhibition or activation.

Aim: The pharmaceutical industry is showing renewed interest in therapeutic peptides. Unfortunately, the chemical synthesis of peptides remains very expensive and problematic in terms of environmental sustainability. Hence, making peptides ‘greener’ has become a new front line for the expansion of peptide market. Results: We developed a mechanochemical solvent-free peptide bond-forming protocol using standard reagents and nanocrystalline hydroxyapatite as a bio-compatible, reusable inorganic base. The reaction was also conducted under ultra-mild, minimal solvent-grinding conditions, using common laboratory equipment. Conclusion: The efficacy of the described protocol was validated with the convenient preparation of endomorphin-1, H-Tyr-Pro-Trp-Phe-NH2, the endogenous ligand of the μ-opioid receptor, currently regarded as a lead for the discovery of painkillers devoid of harmful side effects.

Most anticancer agents are hydrophobic and can easily penetrate the tumor cell membrane by passive diffusion. This may impede the development of highly effective and tumor‐selective treatment options. A hydrophilic β‐glucuronidase‐cleavable linker was used to connect the highly potent antimitotic agent cryptophycin‐55 glycinate with the α v β 3 integrin ligand c (RGDfK). Incorporation of the self‐immolative linker containing glucuronic acid results in lower cytotoxicity than that of the free payload, suggesting that hydrophilic sugar linkers can preclude passive cellular uptake. In vitro drug‐release studies and cytotoxicity assays demonstrated the potential of this small molecule–drug conjugate, providing guidance for the development of therapeutics containing hydrophobic anticancer drugs.

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-(R)-isoAsp(NHPr)-Gly-OH (12) and MPUPA-Dap(Ac)-Gly-OH (13) (MPUPA, methylphenylureaphenylacetic acid; Dap, 2,3-diamino propionic acid). Modification of 12 and 13 by introduction of flexible linkers at isoAsp or Dap gave 49 and 50, 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.

Integrin receptors mediate cell–cell interactions via the recognition of cell-adhesion glycoproteins, as well as via the interactions of cells with proteins of the extracellular matrix, and upon activation they transduce signals bi-directionally across the cell membrane. In the case of injury, infection, or inflammation, integrins of β2 and α4 families participate in the recruitment of leukocytes, a multi-step process initiated by the capturing of rolling leukocytes and terminated by their extravasation. In particular, α4β1 integrin is deeply involved in leukocyte firm adhesion preceding extravasation. Besides its well-known role in inflammatory diseases, α4β1 integrin is also involved in cancer, being expressed in various tumors and showing an important role in cancer formation and spreading. Hence, targeting this integrin represents an opportunity for the treatment of inflammatory disorders, some autoimmune diseases, and cancer. In this context, taking inspiration from the recognition motives of α4β1 integrin with its natural ligands FN and VCAM-1, we designed minimalist α/β hybrid peptide ligands, with our approach being associated with a retro strategy. These modifications are expected to improve the compounds’ stability and bioavailability. As it turned out, some of the ligands were found to be antagonists, being able to inhibit the adhesion of integrin-expressing cells to plates coated with the natural ligands without inducing any conformational switch and any activation of intracellular signaling pathways. An original model structure of the receptor was generated using protein–protein docking to evaluate the bioactive conformations of the antagonists via molecular docking. Since the experimental structure of α4β1 integrin is still unknown, the simulations might also shed light on the interactions between the receptor and its native protein ligands.