Tripeptides Featuring Dehydrophenylalanine and Homophenylalanine: Homo- Versus Hetero-Chirality and Sequence Effects on Self-Assembly and Gelation.

Over the years, our research group developed dehydrodipeptides -capped with aromatic moieties as protease-resistant efficacious hydrogelators, affording self-assembled hydrogels at low (critical) concentrations. Dehydrotripeptides, with different dipeptide sequences and (,) stereochemistry, open a wider chemical space for the development of self-assembled soft nanomaterials. In this work, a small library of -succinylated dehydrotripeptides containing a -terminal dehydrophenylalanine (∆Phe) residue and a scrambled dipeptide sequence with phenylalanine (Phe) and homophenylalanine (Hph) (-Phe-,-Hph and ,-Hph--Phe) was synthesized and characterized as a potential hydrogelator.

Synthesis of - and ,-Heterocycle-Dipeptide Conjugates for Supramolecular Hydrogel Formation.

Small peptides with aromatic nuclei at the -terminus have been shown to form bioactive, biocompatible, and biodegradable supramolecular peptide hydrogels. Novel heterocycle-dipeptide conjugates with potential biological activity or application as drug carriers were synthesized by using (benzo[]thiophene) and ,(thieno [2,3-]pyridine and thieno[2,3-]quinoline) heterocycles as -protective groups for dipeptides l-Phe-l-Phe and l-Phe-l-Leu. The synthesis involved coupling heterocyclic carboxylic acids with trifluoroacetate salts of ethyl l-phenylalanyl-l-phenylalaninate and ethyl l-phenylalanyl- l-leucinate using HBTU and EtN, producing the corresponding six -heterocycle-dipeptide ester conjugates, which were then hydrolyzed to the carboxylic acids.

New Supramolecular Hydrogels Based on Diastereomeric Dehydrotripeptide Mixtures for Potential Drug Delivery Applications.

Self-assembly of peptide building blocks offers unique opportunities for bottom-up preparation of exquisite nanostructures, nanoarchitectures, and nanostructured bulk materials, namely hydrogels. In this work we describe the synthesis, characterization, gelation, and rheological properties of new dehydrotripeptides, Cbz--Lys(Cbz)-,-Asp-∆Phe-OH and (2-Naph)--Lys(2-Naph)-,-Asp-∆Phe-OH, containing a -terminal lysine residue --capped with carboxybenzyl (Cbz) and 2-Naphthylacetyl (2-Naph) aromatic moieties, an aspartic acid residue (Asp), and a -terminal dehydrophenylalanine (∆Phe) residue. The dehydrotripeptides were obtained as diastereomeric mixtures (,, and ,,Z), presumably via aspartimide chemistry.

Development of a dextrin-vitamin D3 micelle nanocarrier for the antimicrobial peptide LLKKK18 as a potential therapeutic agent for bone infections.

In this work, an expedite synthesis was developed for a self-assembled micelle carrier for the antimicrobial peptide LL18. Covalent one-pot functionalization of dextrin with succinylated vitamin D3 and succinic anhydride produced an amphiphilic material that undergoes self-assembly into micelles in aqueous medium. Succinylated dextrin-vitamin D3 micelles were efficiently loaded with LL18 by electrostatic and hydrophobic interactions.

Multifunctional magneto-plasmonic lipogel based on peptide hydrogel for application in combined cancer therapy.

Supramolecular hydrogels, particularly low-molecular-weight peptide hydrogels, are promising drug delivery systems due to their ability to change the solubility, targeting, metabolism and toxicity of drugs. Magneto-plasmonic liposomes, in addition to being remotely controllable with the application of an external magnetic field, also increase the efficiency of encapsulated drug release through thermal stimulation, for example, with magnetic and optical hyperthermia. Thus, the combination of those two materials-giving magneto-plasmonic lipogels-brings together several functionalities, among which are hyperthermia and spatiotemporally controlled drug delivery.

Small Bowel Obstruction by a Phytobezoar in a Patient With Previous Antrectomy and Billroth II Reconstruction.

A phytobezoar is a conglomerate of improperly digested fruit and vegetable debris, and its development is associated, amongst other factors, with previous gastric surgery. Most phytobezoars remain asymptomatic and are incidentally found during imaging or interventional procedures. However, in some patients, they can cause small bowel obstruction, which can subsequently lead to severe complications.

Unveiling the Role of Capping Groups in Naphthalene N-Capped Dehydrodipeptide Hydrogels.

Self-assembled peptide-based hydrogels are archetypical nanostructured materials with a plethora of foreseeable applications in nanomedicine and as biomaterials. N-protected di- and tri-peptides are effective minimalist (molecular) hydrogelators. Independent variation of the capping group, peptide sequence and side chain modifications allows a wide chemical space to be explored and hydrogel properties to be tuned.

Fisetin derivatives exhibit enhanced anti-inflammatory activity and modulation of endoplasmic reticulum stress.

Inflammation and endoplasmic reticulum (ER) stress are often hand in hand in the context of chronic disease. Both are activated upon perceived disturbances in homeostasis, being deleterious when intensely or chronically activated. Fisetin (FST) is a dietary flavonol that is known to possess multiple relevant bioactivities, raising the question of its potential health benefits and even its use in novel pharmacological approaches against ER stress and inflammation.

Peptide-Based Supramolecular Hydrogels as Drug Delivery Agents: Recent Advances.

Supramolecular peptide hydrogels have many important applications in biomedicine, including drug delivery applications for the sustained release of therapeutic molecules. Targeted and selective drug administration is often preferential to systemic drug delivery, as it can allow reduced doses and can avoid the toxicity and side-effects caused by off-target binding. New discoveries are continually being reported in this rapidly developing field.

Mesenteric Schwannoma, Intestinal Malrotation and Ileal Diverticulum: A Unique Association.

Mesenteric schwannomas are rare benign tumors that arise in the mesentery. Ileal diverticula and intestinal malrotation in adults are rare findings, since they are usually asymptomatic. We present the case of an 86-year-old man, without any known previously known medical conditions, who was admitted in the emergency department with recurrent abdominal distension and intense pain.

An injectable, naproxen-conjugated, supramolecular hydrogel with ultra-low critical gelation concentration-prepared from a known folate receptor ligand.

Short peptides capped on the N-terminus with aromatic groups are often able to form supramolecular hydrogels-self-assembled networks of fibrils able to trap water molecules. Typically, these hydrogelators can form stiff gels at concentrations of 0.1 to 1.

Wilkie's Syndrome: An Unexpected Finding.

Wilkie's syndrome is a rare pathology caused by extrinsic compression of the third part of the duodenum by the superior mesenteric artery (SMA) at its origin. The symptoms are variable and non-specific consisting of postprandial abdominal pain, nausea and vomiting, early satiety, anorexia, and weight loss. A contrast-enhanced CT scan is the standard imaging modality.

Initial Screening of Poly(ethylene glycol) Amino Ligands for Affinity Purification of Plasmid DNA in Aqueous Two-Phase Systems.

Gene therapy and DNA vaccination are among the most expected biotechnological and medical advances for the coming years. However, the lack of cost-effective large-scale production and purification of pharmaceutical-grade plasmid DNA (pDNA) still hampers their wide application. Downstream processing, which is mainly chromatography-based, of pDNA remains the key manufacturing step.

Complexes of Bifunctional DO3A-N-(α-amino)propinate Ligands with Mg(II), Ca(II), Cu(II), Zn(II), and Lanthanide(III) Ions: Thermodynamic Stability, Formation and Dissociation Kinetics, and Solution Dynamic NMR Studies.

The thermodynamic, kinetic, and structural properties of Ln complexes with the bifunctional DO3A-ACE ligand and its amide derivative DO3A-BACE (modelling the case where DO3A-ACE ligand binds to vector molecules) have been studied in order to confirm the usefulness of the corresponding Gd complexes as relaxation labels of targeted MRI contrast agents. The stability constants of the Mg and Ca complexes of DO3A-ACE and DO3A-BACE complexes are lower than for DOTA and DO3A, while the Zn and Cu complexes have similar and higher stability than for DOTA and DO3A complexes. The stability constants of the Ln(DO3A-BACE) complexes increase from Ce to Gd but remain practically constant for the late Ln ions (represented by Yb).

Bolaamphiphilic Bis-Dehydropeptide Hydrogels as Potential Drug Release Systems.

The self-assembly of nanometric structures from molecular building blocks is an effective way to make new functional materials for biological and technological applications. In this work, four symmetrical bolaamphiphiles based on dehydrodipeptides (phenylalanyldehydrophenylalanine and tyrosyldehydrophenylalanine) linked through phenyl or naphthyl linkers (terephthalic acid and 2,6-naphthalenedicarboxylic acid) were prepared, and their self-assembly properties were studied. The results showed that all compounds, with the exception of the bolaamphiphile of tyrosyldehydrophenylalanine and 2,6-naphthalene dicarboxylic acid, gave self-standing hydrogels with critical gelation concentrations of 0.

Dehydropeptide Supramolecular Hydrogels and Nanostructures as Potential Peptidomimetic Biomedical Materials.

Supramolecular peptide hydrogels are gaining increased attention, owing to their potential in a variety of biomedical applications. Their physical properties are similar to those of the extracellular matrix (ECM), which is key to their applications in the cell culture of specialized cells, tissue engineering, skin regeneration, and wound healing. The structure of these hydrogels usually consists of a di- or tripeptide capped on the -terminus with a hydrophobic aromatic group, such as Fmoc or naphthalene.

Evaluation of a Model Photo-Caged Dehydropeptide as a Stimuli-Responsive Supramolecular Hydrogel.

Short peptides capped on the -terminus with aromatic groups are often able to form supramolecular hydrogels, via self-assembly, in aqueous media. The rheological properties of these readily tunable hydrogels resemble those of the extracellular matrix (ECM) and therefore have potential for various biological applications, such as tissue engineering, biosensors, 3D bioprinting, drug delivery systems and wound dressings. We herein report a new photo-responsive supramolecular hydrogel based on a "caged" dehydropeptide (CNB-Phe-ΔPhe-OH ), containing a photo-cleavable carboxy-2-nitrobenzyl (CNB) group.

Impact of Citrate and Lipid-Functionalized Magnetic Nanoparticles in Dehydropeptide Supramolecular Magnetogels: Properties, Design and Drug Release.

Currently, the nanoparticle functionalization effect on supramolecular peptide-based hydrogels remains undescribed, but is expected to affect the hydrogels' self-assembly and final magnetic gel properties. Herein, two different functionalized nanoparticles: citrate-stabilized (14.4 ± 2.

Exploring the properties and potential biomedical applications of NSAID-capped peptide hydrogels.

The development of strategies to minimise the adverse side-effects of non-steroidal anti-inflammatory drugs (NSAIDs) remains a challenge for medicinal chemists. One such strategy is the development of NSAID-peptide prodrug conjugates and this conjugation to a peptide often confers the additional property of hydrogelation. This review summarises the work published by our research group, alongside other research groups, on supramolecular hydrogels consisting of short peptides conjugated to NSAIDs.

Older adults with physical disabilities: vulnerabilities relative to the body, the physical and social environment.

Objective: to understand the vulnerabilities of older adults with physical disabilities regarding their body, physical and social environments.

Method: this was a qualitative study based on Alfred Schütz' social phenomenology, with 15 older adults with physical disability from Cuiabá, state of Mato Grosso, Brazil. Open-ended questionnaires were administered to the participants in 2017.

Cecal Perforation by a Large Gallstone: An Unusual Diagnosis.

Cholecystocolic fistulas are uncommon, with rare cases of colonic obstruction described in the literature and even rarer cases of intestinal perforation due to gallstones. We describe a case of a 73-year-old man who presented to our ED with complaints of diffuse abdominal pain, vomiting, constipation, and fever for the past week. Abdomen CT showed signs of acute perforated appendicitis.

Biological Evaluation of Naproxen-Dehydrodipeptide Conjugates with Self-Hydrogelation Capacity as Dual LOX/COX Inhibitors.

The use of peptide-drug conjugates is emerging as a powerful strategy for targeted drug delivery. Previously, we have found that peptides conjugated to a non-steroidal anti-inflammatory drug (NSAID), more specifically naproxen-dehydrodipeptide conjugates, readily form nanostructured fibrilar supramolecular hydrogels. These hydrogels were revealed as efficacious nano-carriers for drug delivery applications.

Magnetic Dehydrodipeptide-Based Self-Assembled Hydrogels for Theragnostic Applications.

Self-assembled peptide hydrogels have emerged in recent years as the new paradigm in biomaterials research. We have contributed to this field the development of hydrogels based on dehydrodipeptides -capped with naproxen. The dehydrodipeptide hydrogels can be loaded with drugs, thus being potential nanocarriers for drug delivery.

Self-assembled RGD dehydropeptide hydrogels for drug delivery applications.

Peptide-based self-assembled hydrogels have triggered remarkable research interest in recent years owing to their biocompatibility and biomimetic properties and responsiveness, which warrant many technological and biomedical applications. Dehydrodipeptides N-capped with naproxen emerged from our research as effective hydrogelators endowed with resistance to proteolysis. Dehydrodipeptide-based hydrogels are promising nanocarriers for drug delivery applications.