Search results for "combinatorial"
showing 10 items of 1208 documents
Pentafluorophenyl Ester-based Polymersomes as Nanosized Drug-Delivery Vehicles
2015
In this work, activated ester chemistry is employed to synthesize biocompatible and readily functionalizable polymersomes. Via aminolysis of pentafluorophenyl methacrylate-based precursor polymers, an N-(2-hydroxypropyl) methacrylamide (HPMA)-analog hydrophilic block is obtained. The precursor polymers can be versatile functionalized by simple addition of suitable primary amines during aminolysis as demonstrated using a fluorescent dye. Vesicle formation is proven by cryoTEM and light scattering. High encapsulation efficiencies for hydrophilic cargo like siRNA are achieved using dual centrifugation and safe encapsulation is demonstrated by gel electrophoresis. In vitro studies reveal low cy…
Selective recognition of small hydrogen bond acceptors by a calix[6]arene-based molecular container
2019
Selective molecular recognition is of primary importance for applications such as sensing and separation of chemicals. This work describes the host-guest and crystallisation properties of a penta-carbamated calix[6]arene designed as a molecular container with a H-donating recognition group directed towards the heart of the cavity. As demonstrated by NMR spectroscopy and X-ray diffraction studies, this macrocyclic receptor can selectively recognise small H-bond acceptors through one or two hydrogen bonds, the guests nesting inside the polyaromatic cavity surrounded by eleven bulky tert-butyl groups.
Efficient Synthesis of Multifunctional Chelating Agents Based on Tetraazacycloalkanes
2018
An efficient route has been developed for the synthesis of multifunctional tetraazacycloalkanes (in particular 1,4,7,10-tetraazacyclotridecane) incorporating an aminomethyl pendant arm on the carbon skeleton. Starting from the appropriate C-functionalized bisaminal-protected intermediate, the target macrocycles were easily obtained by means of a step-by-step introduction of the desired functional groups onto the free primary amine group, followed by deprotection of the bisaminal intermediates. This straightforward and versatile synthetic approach paves the way for the design of a new family of multifunctional chelators.
Development of functionalized SYBR green II related cyanine dyes for viral RNA detection
2020
Abstract Fluorescent probes for sensing nucleic acids have found widespread use in the field of cell and molecular biology. However, probes combined with potential for post-synthetic conjugation, e.g. for intra-endosomal measurements of RNA, are unavailable. Herein we developed cyanine dyes that can be conjugated to viral capsid or other targets. First, we solved the crystal structure of SYBR Green II. The structural elucidation of this commonly used RNA probe provided the basis for synthesizing similar molecules with much desired function for post-synthetic conjugation. To address this need, cyanine dyes were prepared using an alternative synthesis protocol. All studied compounds showed co…
The Use of Rule-Based and QSPR Approaches in ADME Profiling: A Case Study on Caco-2 Permeability.
2013
During the early ADME profiling the development of simple, interpretable and reliable in silico tools is very important. In this study, rule-based and QSPR approaches were investigated using a large Caco-2 permeability database. Three permeability classes were determined: high (H), moderate (M) and low (L). The main physicochemical properties related with permeability were ranked as follows: Polar Surface Area (PSA)>Lipophilicity (logP/logD)>Molecular Weight (MW)>number of Hydrogen Bond donors and acceptors>Ionization State>number of Rotatable Bonds>number of Rings. The best rule, based on the combination of PSA-MW-logD (3PRule), was able to identify the H, M and L classes with accuracy of …
One-Pot Synthesis of Pyrrole-2-carboxylates and -carboxamides via an Electrocyclization/Oxidation Sequence
2014
An electrocyclic ring closure is the key step of an efficient one-pot method for the synthesis of pyrrole-2-carboxylates and -carboxamides from chalcones and glycine esters or amides. The 3,4-dihydro-2H-pyrrole intermediates generated in situ are oxidized to the corresponding pyrroles by stoichiometric oxidants or by catalytic copper(II) and air in moderate to high yields. A wide range of functional groups are tolerated, and further combination with an in situ bromination gives access to polyfunctional pyrrole scaffolds.
Development of rhodesain inhibitors with a 3-bromoisoxazoline warhead
2013
Novel rhodesain inhibitors were obtained by combining an enantiomerically pure 3-bromoisoxazoline warhead with a specific peptidomimetic recognition moiety. All derivatives behaved as inhibitors of rhodesain, with low micromolar Ki values. Their activity against the enzyme was found to be paralleled by an in vitro antitrypanosomal activity, with IC50 values in the mid-micromolar range. Notably, a preference for parasitic over human proteases, specifically cathepsins B and L, was observed.
Optimization of peptidomimetic boronates bearing a P3 bicyclic scaffold as proteasome inhibitors
2014
Abstract A new series of pseudopeptide boronate proteasome inhibitors (2–3) was developed, through optimization of our previously described analogs of bortezomib, bearing a bicyclic 1,6-naphthyridin-5(6H)-one scaffold as P3 fragment (1). The biological evaluation on human 20S proteasome displayed a promising inhibition profile, especially for compounds bearing a P2 ethylene fragment, which exhibited Ki values in the nanomolar range for the ChT-L activity (e.g. 2a, Ki = 0.057 μM) and considerable selectivity for proteasome over bovine pancreatic α-chymotrypsin. Docking experiments into the yeast 20S proteasome revealed that the ligands are accommodated predominantly into the ChT-L site and t…
The Recent Crystal Structure of Human Tyrosinase Related Protein 1 (HsTYRP1) Solves an Old Problem and Poses a New One
2017
Show your metal: l-Tyrosine is converted into the protective antioxidative polymer melanin in a sequence of reactions. In humans, the catalytic pathway starts with the tyrosinase HsTYR and two tyrosinase-related proteins HsTYRP1 and HsTYRP2. All three enzymes have the same active site but the latter two contain two zinc ions instead of copper ions.
According to the CPLL proteome sheriffs, not all aperitifs are created equal!
2014
Combinatorial peptide ligand libraries (CPLLs) have been adopted for investigating the proteome of a popular aperitif in Northern Italy, called "Amaro Branzi", stated to be an infusion of a secret herbal mixture, of which some ingredients are declared on the label, namely Angelica officinalis, Gentiana lutea and orange peel, sweetened by a final addition of honey. In order to assess the genuineness of this commercial liqueur, we have prepared extracts of the three vegetable ingredients, assessed their proteomes, and compared them to the one found in the aperitif. The amaro's proteome was identified via prior capture with CPLLs at two different pH values (2.2 and 4.8). Via mass spectrometry …