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1.
ACS Polym Au ; 4(3): 214-221, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38882036

ABSTRACT

A microwave-assisted esterification reaction to prepare hyaluronan-curcumin derivatives by employing a solvent-free process was developed. In particular, a solid-state strategy to react two molecules characterized by totally different solubility profiles was developed. Hyaluronic acid, a highly hydrosoluble polysaccharide, was reacted with hydrophobic and even water-unstable curcumin. Microwave (MW) irradiation was employed to activate the reaction between the two solid compounds through the direct interaction with them and to preserve the integrity of the sensitive curcumin species. This new protocol can be considered efficient, fast, and also eco-friendly, avoiding the employment of toxic organic bases and solvents. A cytotoxicity test suggested that the developed hyaluronan-curcumin conjugate (HA-CUR) could be considered a candidate for its implementation as a new material. In addition, preliminary studies revealed promising anti-inflammatory activity and open future perspectives of further investigation.

2.
J Funct Biomater ; 14(1)2023 Jan 02.
Article in English | MEDLINE | ID: mdl-36662073

ABSTRACT

Promoting bone healing is a key challenge in our society that can be tackled by developing new implantable biomaterials provided with regenerative properties. In this work, the coating of three-dimensional porous glass-derived scaffolds with hyaluronic acid (HA)-fatty acids was investigated for the first time. The starting scaffolds, based on bioactive silicate glass, were produced by foam replication followed by sintering; then, HA-palmitate and HA-oleate conjugate coatings were deposited on the scaffold struts through a dipping procedure. FT-IR analysis confirmed the successful deposition of the coatings on the surface and struts of the scaffolds, the foam-like architecture of which was maintained as assessed by SEM investigations. The in vitro bioactivity of the HA-fatty-acid-coated scaffolds was studied by immersion tests in simulated body fluid and the subsequent evaluation of hydroxyapatite formation. The deposition of the polymeric coating did not inhibit the apatite-forming ability of scaffolds, as revealed by the formation of nanostructured hydroxyapatite agglomerates 48 h from immersion. These promising results motivate further investigation of these novel bioactive systems, which are expected to combine the bone-bonding properties of the glass with the wound-healing promotion carried out by the polymeric conjugates.

3.
ACS Med Chem Lett ; 13(5): 807-811, 2022 May 12.
Article in English | MEDLINE | ID: mdl-35586438

ABSTRACT

A recently developed synthetic protocol allowed for the functionalization of the active peptide A9 with a fluorogenic probe, which is useful for studying biomolecular interactions. Essentially, a nucleophilic attack on a halo-substituted benzofurazan is selectively performed by a cysteine sulfhydryl group. The process is assisted by the basic catalysis of activated zeolites (4 Å molecular sieves) and promoted by microwave irradiation. Fluorescence studies revealed that a donor-acceptor pair within the peptide sequence was introduced, thus allowing a deeper investigation on the interaction process between the peptide ligand and its receptor fragment. The obtained results allowed us to come full circle for all the currently understood structural determinants that were found to be involved in the binding process.

4.
Molecules ; 26(20)2021 Oct 11.
Article in English | MEDLINE | ID: mdl-34684715

ABSTRACT

Aziridine derivatives involved in nucleophilic ring-opening reactions have attracted great interest, since they allow the preparation of biologically active molecules. A chemoselective and mild procedure to convert a peptide cysteine residue into lanthionine via S-alkylation on aziridine substrates is presented in this paper. The procedure relies on a post-synthetic protocol promoted by molecular sieves to prepare lanthionine-containing peptides and is assisted by microwave irradiation. In addition, it represents a valuable alternative to the stepwise approach, in which the lanthionine precursor is incorporated into peptides as a building block.


Subject(s)
Alanine/analogs & derivatives , Aziridines/chemistry , Chromatography, Gel/methods , Sulfides/chemistry , Alanine/chemistry , Alkylation , Catalysis , Chromatography, Liquid , Cysteine/chemistry , Heating , Microwaves , Molecular Structure , Peptides/chemistry
5.
Int J Mol Sci ; 21(22)2020 Nov 23.
Article in English | MEDLINE | ID: mdl-33238365

ABSTRACT

Identification of molecules able to promote neuroprotective mechanisms can represent a promising therapeutic approach to neurodegenerative disorders including Huntington's disease. Curcumin is an antioxidant and neuroprotective agent, even though its efficacy is limited by its poor absorption, rapid metabolism, systemic elimination, and limited blood-brain barrier (BBB) permeability. Herein, we report on novel biodegradable curcumin-containing nanoparticles to favor the compound delivery and potentially enhance its brain bioavailability. The prepared hyaluronan-based materials able to self-assemble in stable spherical nanoparticles, consist of natural fatty acids chemically conjugated to the natural polysaccharide. The aim of this study is to provide a possible effective delivery system for curcumin with the expectation that, after having released the drug at the specific site, the biopolymer can degrade to nontoxic fragments before renal excretion, since all the starting materials are provided by natural resource. Our findings demonstrate that curcumin-encapsulated nanoparticles enter the cells and reduce their susceptibility to apoptosis in an in vitro model of Huntington's disease.


Subject(s)
Curcumin/pharmacology , Drug Delivery Systems , Huntingtin Protein/genetics , Huntington Disease/drug therapy , Nanoparticles/chemistry , Animals , Antioxidants/chemistry , Antioxidants/pharmacology , Blood-Brain Barrier/drug effects , Cell Line , Curcumin/chemistry , Gene Expression Regulation/drug effects , Humans , Huntington Disease/genetics , Huntington Disease/pathology , Hyaluronic Acid/chemistry , Hyaluronic Acid/pharmacology , Mice , Neuroprotective Agents/chemistry , Neuroprotective Agents/pharmacology , Spectroscopy, Fourier Transform Infrared , Surface-Active Agents/chemistry , Surface-Active Agents/pharmacology
6.
J Med Chem ; 63(24): 15333-15343, 2020 12 24.
Article in English | MEDLINE | ID: mdl-33226807

ABSTRACT

A short (Fab)trastuzumab-derived peptide specific for HER2 receptor was identified. Its affinity for the model system HER2-DIVMP was found in a nanomolar range. The structural determinants responsible for the interaction between this ligand (A9) and HER2-DIVMP were investigated by both computational and NMR analysis. Next, the possibility of using A9 as HER2- specific probe for the nuclear medicine imaging was evaluated by conjugating A9 with the DTPA chelator and radiolabeling it with 111In. The developed probe retained a nanomolar affinity to HER2-overexpressing cancer cells, however, some unspecific binding also occurred. The peptide internalization into cells by receptor-mediated endocytosis was also studied. Future perspectives are aimed at using A9 as a probe for molecular imaging diagnostics as well as active targeting of anticancer drugs. Lead structure optimization is needed to minimize the percentage of A9 unspecific binding and to increase the binding affinity to the receptor.


Subject(s)
Peptides/chemistry , Receptor, ErbB-2/metabolism , Animals , Binding Sites , Humans , Immunoconjugates/chemistry , Immunoconjugates/metabolism , Isotope Labeling , Ligands , Magnetic Resonance Imaging , Molecular Dynamics Simulation , Neoplasms/diagnostic imaging , Neoplasms/metabolism , Neoplasms/pathology , Pentetic Acid/chemistry , Peptides/metabolism , Protein Binding , Receptor, ErbB-2/agonists , Receptor, ErbB-2/antagonists & inhibitors , Tissue Distribution , Trastuzumab/chemistry
7.
J Pept Sci ; 26(2): e3231, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31749266

ABSTRACT

The binding process of A9 peptide toward HER2-DIVMP, a synthetic model of the receptor domain IV, was studied by using the surface plasmon resonance (SPR) technique, with the aim of validating it as a fast and reliable screening method for selecting peptide ligands specifically targeting a domain of their target. To investigate the structural basis of A9 binding to the model of HER2-DIVMP, multiple ligand-based nuclear magnetic resonance (NMR) methods were applied. The use of saturation transfer difference (STD) and WaterLOGSY NMR experiments identified key residues in the peptide for the receptor binding. Moreover, the bound conformation of the A9 peptide was obtained using transferred nuclear Overhauser effect spectroscopy (trNOESY) experiments. The NMR data revealed an extended binding surface that confirms an in silico model previously reported. These structural findings could provide good starting points for future lead structures optimization specific for the receptor target.


Subject(s)
Peptides/chemistry , Peptides/pharmacology , Receptor, ErbB-2/metabolism , Magnetic Resonance Spectroscopy , Protein Binding , Protein Domains , Receptor, ErbB-2/chemistry , Surface Plasmon Resonance
8.
J Org Chem ; 84(22): 14957-14964, 2019 11 15.
Article in English | MEDLINE | ID: mdl-31625377

ABSTRACT

A green and efficient method for preparing lanthionine peptides by a highly chemoselective and stereochemically controlled procedure is presented. It involves an S-alkylation reaction, promoted by activated molecular sieves, on chiral cyclic sulfamidates, both N-protected and unprotected. Of note, the reaction yield was high also for cyclic sulfamidates bearing a free amine group, while other strategies failed to achieve a ring-opening nucleophilic reaction with N-unprotected substrates. To prove the feasibility of the procedure, the synthesis of a thioether ring B mimetic of the natural lantibiotic haloduracin ß was performed.


Subject(s)
Alanine/analogs & derivatives , Peptides/chemistry , Sulfides/chemical synthesis , Sulfonic Acids/chemistry , Alanine/chemistry , Alkylation , Molecular Structure , Sulfides/chemistry
9.
Org Lett ; 20(23): 7478-7482, 2018 12 07.
Article in English | MEDLINE | ID: mdl-30427200

ABSTRACT

A one-pot, high-yield procedure for synthesizing lanthionine-containing peptides was developed. It relies on the S-alkylation of cysteine-containing peptides with chiral cyclic sulfamidates. The key feature of this approach is the use of mild reaction conditions (only activated molecular sieves are employed as the catalyst), leading to good chemoselectivity and excellent stereochemical control. The potential of the new methodology has been investigated by synthesizing the thioether ring of a natural lantibiotic, Haloduracin ß.


Subject(s)
Alanine/analogs & derivatives , Peptides/chemical synthesis , Sulfides/chemistry , Sulfonic Acids/chemistry , Alanine/chemistry , Alkylation , Molecular Conformation , Peptides/chemistry
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