A5074361625- Monoclonal and Polyclonal Antibodies Research
- Hepatitis C virus research
- Pregnancy-related medical research
- Chemical Synthesis and Analysis
- Peptidase Inhibition and Analysis
- Antimicrobial Peptides and Activities
- Cholesterol and Lipid Metabolism
- Peroxisome Proliferator-Activated Receptors
- Biochemical and Structural Characterization
- Click Chemistry and Applications
- Genomics, phytochemicals, and oxidative stress
- Glycosylation and Glycoproteins Research
- Synthesis and Biological Evaluation
- Histone Deacetylase Inhibitors Research
- Endometriosis Research and Treatment
- Drug Transport and Resistance Mechanisms
- Toxin Mechanisms and Immunotoxins
- Genetic Neurodegenerative Diseases
- Alzheimer's disease research and treatments
- Biochemical and Molecular Research
- Nerve injury and regeneration
- Protein purification and stability
- Mitochondrial Function and Pathology
- PARP inhibition in cancer therapy
- Injury Epidemiology and Prevention
IRBM Science Park
2000-2025
Merck & Co., Inc., Rahway, NJ, USA (United States)
2009
United States Military Academy
2000
Institute of Molecular Biology and Pathology
1998
α‐Synuclein (α‐syn) protein and a fragment of it, called NAC, have been found in association with the pathological lesions number neurodegenerative diseases. Recently, mutations α‐syn gene reported families susceptible to an inherited form Parkinson's disease. We shown that human wild‐type α‐syn, mutant α‐syn(Ala30Pro) α‐syn(Ala53Thr) proteins can self‐aggregate amyloid‐like filaments. Here we report aggregates NAC induced apoptotic cell death neuroblastoma SH‐SY5Y cells. These findings...
Peptide C-terminal thioesters are key intermediates in a variety of applications, most notably the recently developed native chemical ligation methods for total synthesis proteins. So far they have been prepared only by use least prevalent Boc/benzyl solid-phase method on ad hoc resin supports. We describe here novel solid phase Fmoc/t-Bu method. The is based 3-carboxypropanesulfonamide safety-catch linker, which fully stable to repetitive exposure basic conditions needed Fmoc cleavage....
In the absence of a broadly effective cure for hepatitis caused by C virus (HCV), much effort is currently devoted to search inhibitors virally encoded protease NS3. This chymotrypsin-like serine required maturation viral polyprotein, cleaving it at NS3−NS4A, NS4A−NS4B, NS4B−NS5A, and NS5A−NS5B sites. course our studies on substrate specificity NS3, we found that products cleavage corresponding P6−P1 region substrates act as competitive enzyme, with IC50s ranging from 360 1 μM. A detailed...
The therapeutic potential of relaxin for heart failure and renal disease in clinical trials is hampered by the short half-life serelaxin. Optimization fatty acid-acetylated single-chain peptide analogues culminated design synthesis R2R01, a potent selective RXFP1 agonist with subcutaneous bioavailability extended half-life.
Peptide 1, a C18 fatty acid-modified single-chain relaxin analogue, was recently identified as potent, selective, and long-lasting family peptide receptor 1 (RXFP1) agonist. Further advanced pharmacokinetic profiling of this compound highlighted elevated levels oxidative metabolism occurring in dogs mini pigs but only marginally rats. This study aimed to design analogues with increased stability against metabolic oxidation while securing subnanomolar RXFP1 potency. Key structural elements,...
The insulin-like peptide human relaxin-2 was identified as a hormone that, among other biological functions, mediates the hemodynamic changes occurring during pregnancy. Recombinant (serelaxin) has shown beneficial effects in acute heart failure, but its full therapeutic potential been hampered by short half-life and need for intravenous administration limiting use to intensive care units. In this study, we report development of long-acting potent single-chain relaxin mimetics. Modifications...
Abstract Previously, we identified a potent antimicrobial analogue of temporin L (TL), [Pro 3 ]TL, in which glutamine at position was substituted with proline. In this study, series analogues is non‐natural proline derivatives, investigated for correlations between the conformational properties compounds and their antibacterial, cytotoxic, hemolytic activities. Non‐natural substituents 4 pyrrolidine ring were considered. Structure–activity relationship (SAR) studies these performed by means...
Abstract Despite beneficial effects in acute heart failure, the full therapeutic potential of recombinant relaxin-2 has been hampered by its short half-life and need for intravenous administration limiting use to intensive care units. A multiparametric optimization relaxin B-chain led identification single chain lipidated peptide agonists RXFP1 like SA10SC-RLX with subcutaneous bioavailability extended half-life. sub nanomolar activity on cells expressing human molecular modeling associated...
ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTEngineering and Chemical Synthesis of a Transmembrane Protein: The HCV Protease Cofactor Protein NS4AElisabetta Bianchi, Raffaele Ingenito, Reyna J. Simon, Antonello PessiView Author Information Istituto di Ricerche Biologia Molecolare P. Angeletti (IRBM), Via Pontina Km 30.600 00040 Pomezia (Rome), Italy Gryphon Sciences, 250 East Grand Avenue South San Francisco, California 94080 Cite this: Am. Chem. Soc. 1999, 121, 33, 7698–7699Publication...
Infection by Hepatitis C Virus (HCV) leads to a slowly progressing disease that over two decades can lead liver cirrhosis or cancer. Currently, one of the most promising approaches anti-HCV therapy is development inhibitors NS3/4A protease, which essential for maturation viral polyprotein. Several substrate-derived have been described, all taking advantage binding S subsite enzyme. Inspection S' shows pockets might be exploited inhibitor binding, but due fact ground-state not used substrate,...
[reaction: see text] Fmoc-protected amino acid fluorides were found to be excellent reagents for the acylation of sulfonamide safety-catch linkers (SCL) suitable subsequent preparation peptide C-terminal thioesters. High loadings obtained on different types resins with low levels epimerization.
One of the most promising approaches to anti-hepatitis C virus drug discovery is development inhibitors virally encoded protease NS3. This chymotrypsin-like serine essential for maturation viral polyprotein, and processing requires complex formation between NS3 its cofactor NS4A. Recently, we reported on potent cleavage product-derived [Ingallinella et al. (1998) Biochemistry 37, 8906−8914]. Here study interaction these with NS3/cofactor complex. Inhibitors bind according an induced-fit...
Surfaces in highly anthropized environments are frequently contaminated by both harmless and pathogenic bacteria. Accidental contact between these surfaces people could contribute to uncontrolled or even dangerous microbial diffusion. Among all possible solutions useful achieve effective disinfection, ultraviolet irradiations (UV) emerge as one of the most "Green" technologies since they can inactivate microorganisms via formation DNA/RNA dimers, avoiding environmental pollution associated...
A serine protease domain contained within the viral NS3 protein is a key player in maturational processing of hepatitis C virus polyprotein and prime target for development antiviral drugs. In present work, we describe dansylated hexapeptide inhibitor this enzyme. Active site occupancy by compound could be monitored following fluorescence resonance energy transfer between dansyl fluorophore tryptophan residues used to 1) unambiguously assess active binding inhibitors, 2) directly determine...
In the present paper, systematic studies revealed that Cu(I) salts in general and Cu(II) under certain circumstances promote effective reaction between peptide thiol esters N-terminal amino function of a second segment to give native amide bond for both solution- solid-phase syntheses. Chiral integrity was retained. Reaction conditions were optimized applied synthesis small protein, identity which confirmed by NMR analysis.