Peptide Derivatives of Retinylamine Prevent Retinal Degeneration with Minimal Side Effects on Vision in Mice.

Safe and effective molecular therapeutics for prophylactic treatment of retinal degenerative diseases are greatly needed. Disruptions in the clearance of all--retinal (atRAL) by the visual (retinoid) cycle of the retina can lead to the accumulation of atRAL and its condensation products known to initiate progressive retinal dystrophy. Retinylamine (Ret-NH) and its analogues are known to be effective in lowering the concentration of atRAL within the eye and thus preventing retinal degeneration in mouse models of human retinopathies.

New GABA modulators protect photoreceptor cells from light-induced degeneration in mouse models.

No clinically approved therapies are currently available that prevent the onset of photoreceptor death in retinal degeneration. Signaling between retinal neurons is regulated by the release and uptake of neurotransmitters, wherein GABA is the main inhibitory neurotransmitter. In this work, novel 3-chloropropiophenone derivatives and the clinical anticonvulsants tiagabine and vigabatrin were tested to modulate GABA signaling and protect against light-induced retinal degeneration.

Manganese-Enhanced MRI for Preclinical Evaluation of Retinal Degeneration Treatments.

Purpose: Apply manganese-enhanced magnetic resonance imaging (MEMRI) to assess ion channel activity and structure of retinas from mice subject to light-induced retinal degeneration treated with prophylactic agents.

Methods: Abca4(-/-)Rdh8(-/-) double knockout mice with and without prophylactic retinylamine (Ret-NH2) treatment were illuminated with strong light. Manganese-enhanced MRI was used to image the retina 2 hours after intravitreous injection of MnCl2 into one eye.

Prolonged prevention of retinal degeneration with retinylamine loaded nanoparticles.

Retinal degeneration impairs the vision of millions in all age groups worldwide. Increasing evidence suggests that the etiology of many retinal degenerative diseases is associated with impairment in biochemical reactions involved in the visual cycle, a metabolic pathway responsible for regeneration of the visual chromophore (11-cis-retinal). Inefficient clearance of toxic retinoid metabolites, especially all-trans-retinal, is considered responsible for photoreceptor cytotoxicity.

Novel quorum-quenching agents promote methicillin-resistant Staphylococcus aureus (MRSA) wound healing and sensitize MRSA to β-lactam antibiotics.

The dwindling repertoire of antibiotics to treat methicillin-resistant Staphylococcus aureus (MRSA) calls for novel treatment options. Quorum-quenching agents offer an alternative or an adjuvant to antibiotic therapy. Three biaryl hydroxyketone compounds discovered previously (F1, F12, and F19; G.

Multifunctional PEG retinylamine conjugate provides prolonged protection against retinal degeneration in mice.

A polyethylene glycol (PEG) retinylamine (Ret-NH2) conjugate PEG-GFL-NH-Ret with a glycine-phenylalanine-leucine (GFL) spacer was synthesized for controlled oral delivery of Ret-NH2 to treat retinal degenerative diseases, including Stargardt disease (STGD) and age-related macular degeneration (AMD). The peptide spacer was introduced for sustained release of the drug by digestive enzymes in the gastrointestinal tract. The pharmacokinetics experiments showed that the PEG conjugate could control the sustained drug release after oral administration and had much lower nonspecific liver drug accumulation than the free drug in wild-type female C57BL mice.

Peptide targeted high-resolution molecular imaging of prostate cancer with MRI.

Non-invasive accurate detection of prostate cancer is critical for clinical management of the disease. Molecular MRI has a potential for accurate detection of prostate cancer with high spatial resolution. Fibronectin is a hallmark of epithelial-mesenchymal transition occurred in aggressive prostate cancer and highly expressed in malignant tumors.

Combinatorial synthesis and in vitro evaluation of a biaryl hydroxyketone library as antivirulence agents against MRSA.

Antibiotic resistance coupled with decreased development of new antibiotics necessitates the search for novel antibacterial agents. Antivirulence agents offer an alternative to conventional antibiotics. In this work, we report on a family of small-molecule antivirulence agents against methicillin-resistant Staphylococcus aureus (MRSA), the most widespread bacterial pathogen.

Synthesis and evaluation of a nanoglobular dendrimer 5-aminosalicylic Acid conjugate with a hydrolyzable schiff base spacer for treating retinal degeneration.

Biocompatible dendrimers with well-defined nanosizes are increasingly being used as carriers for drug delivery. 5-Aminosalicylic acid (5-ASA) is an FDA-approved therapeutic agent recently found effective in treating retinal degeneration of animal models. Here, a water-soluble dendrimer conjugate of 5-ASA (AGFB-ASA) was designed to treat such retinal degeneration.

MR molecular imaging of prostate cancer with a small molecular CLT1 peptide targeted contrast agent.

Tumor extracellular matrix has abundance of cancer related proteins that can be used as biomarkers for cancer molecular imaging. In this work, we demonstrated effective MR cancer molecular imaging with a small molecular peptide targeted Gd-DOTA monoamide complex as a targeted MRI contrast agent specific to clotted plasma proteins in tumor stroma. We performed the experiment of evaluating the effectiveness of the agent for non-invasive detection of prostate tumor with MRI in a mouse orthotopic PC-3 prostate cancer model.

Discovery of antivirulence agents against methicillin-resistant Staphylococcus aureus.

Antivirulence agents inhibit the production of disease-causing virulence factors but are neither bacteriostatic nor bactericidal. Antivirulence agents against methicillin-resistant Staphylococcus aureus (MRSA) strain USA300, the most widespread community-associated MRSA strain in the United States, were discovered by virtual screening against the response regulator AgrA, which acts as a transcription factor for the expression of several of the most prominent S. aureus toxins and virulence factors involved in pathogenesis.

Synthesis and evaluation of a peptide targeted small molecular Gd-DOTA monoamide conjugate for MR molecular imaging of prostate cancer.

Tumor extracellular matrix has an abundance of cancer related proteins that can be used as biomarkers for cancer molecular imaging. Innovative design and development of safe and effective targeted contrast agents to these biomarkers would allow effective MR cancer molecular imaging with high spatial resolution. In this study, we synthesized a low molecular weight CLT1 peptide targeted Gd(III) chelate CLT1-dL-(Gd-DOTA)(4) specific to clotted plasma proteins in tumor stroma for cancer MR molecular imaging.

Regioselective synthesis of novel 3-thiazolidine acetic acid derivatives from glycosido ureides.

A series of 3-thiazolidine acetic acid-2-(per-O-acetylglycosyl)-1'-imino-α-(substituted)-4-oxo ethyl ester derivatives (3a-t) were prepared via the reaction of substituted amino acid-N-[(per-O-acetylglycosylamino)thioxomethyl]-ethyl ester with ethyl bromoacetate. The crystal structure of 3-thiazolidine acetic acid-2-(2',3',4',6'-tetra-O-acetyl-β-D-galactoyranosyl)-1'-imino-α-methyl-4-oxo ethyl ester 3g and ¹H-¹³C HMBC (2D NMR experiments) measurements of 3-thiazolidine acetic acid-2-(2',3',4',6'-tetra-O-acetyl-β-D-galactopyranosyl)-1'-imino-α-(1-methylthio)ethyl-4-oxo ethyl ester 3j revealed the exclusive regioselectivity during the closure of these rings toward the N-2 position of the thiourea moiety. Furthermore, the crystal structure of compound 3g showed that the attack of N-1 was blocked by sugar ring owing to the steric effect.

Synthesis and fungicidal evaluation of 2-arylphenyl ether-3-(1H-1,2,4-triazol-1-yl)propan-2-ol derivatives.

A series of novel 2-arylphenyl ether-3-(1H-1,2,4-triazol-1-yl)propan-2-ol derivatives were designed and synthesized as candidate fungicides. The new compounds were identified by (1)H NMR spectroscopy and element analysis. Their antifungal activities were evaluated.

2-n-Butyl-1,2-benzisothia-zol-3(2H)-one 1,1-dioxide.

The crystal packing of the title compound, C(11)H(13)NO(3)S, exhibits weak inter-molecular C-H⋯O hydrogen bonding, which links mol-ecules related by translation along the b axis into chains, and π-π inter-actions [centroid-centroid distance of 3.778 (2) Å between benzene rings].

7-Nitro-quinazolin-4(3H)-one.

In the crystal structure of the title compound, C(8)H(5)N(3)O(3), inter-molecular N-H⋯O hydrogen bonds link mol-ecules into centrosymmetric dimers. These dimers are, in turn, linked though weak inter-molecular C-H⋯O and C-H⋯N hydrogen bonds and π-π stacking inter-actions, with centroid-centroid distances of 3.678 (3) Å, into a three-dimensional network.