Search results for "rational design"
showing 10 items of 63 documents
Rational Design of Latent Fluorophores from Water-Soluble Hydroxyphenyltriazine Dyes Suitable for Lipase Sensing
2015
The phenol residue of water‐soluble 2‐(2′‐hydroxy‐5′‐dimethylaminobenzyl)‐4,6‐dimethylamino‐1,3,5‐triazine is masked by an enzyme‐labile protecting group constructed with a self‐immolative para‐hydroxybenzyl alcohol. The fluorescence of the dyes is restored with lipases under physiological conditions without aggregation or precipitation of the fluorescent dyes. Derivatives of 2‐(2′‐hydroxy‐5′‐dimethylaminobenzyl)‐4,6‐dimethylamino‐1,3,5‐triazine were synthesized by an original multistep protocol that afforded, after quaternization of the N,N‐dimethylaminobenzyl moiety, water‐soluble fluorescent dyes. These fluorophores exhibited excited‐state intramolecular proton transfer and large Stokes …
Theoretical studies of HIV-1 reverse transcriptase inhibition
2012
Computational methods for accurately calculating the binding affinity of a ligand for a protein play a pivotal role in rational drug design. We herein present a theoretical study of the binding of five different ligands to one of the proteins responsible for the human immunodeficiency virus type 1 (HIV-1) cycle replication; the HIV-1 reverse transcriptase (RT). Two types of approaches are used based on molecular dynamics (MD) simulations within hybrid QM/MM potentials: the alchemical free energy perturbation method, FEP, and the pathway method, in which the ligand is physically pulled away from the binding site, thus rendering a potential of mean force (PMF) for the binding process. Our com…
A synthetic hexapeptide (Argireline) with antiwrinkle activity
2008
Botulinum neurotoxins (BoNTs) represent a revolution in cosmetic science because of their remarkable and long-lasting antiwrinkle activity. However, their high neurotoxicity seriously limits their use. Thus, there is a need to design and validate non-toxic molecules that mimic the action of BoNTs. The hexapeptide Ac-EEMQRR-NH2 (coined Argireline) was identified as a result of a rational design programme. Noteworthy, skin topography analysis of an oil/water (O/W) emulsion containing 10% of the hexapeptide on healthy women volunteers reduced wrinkle depth up to 30% upon 30 days treatment. Analysis of the mechanism of action showed that Argireline significantly inhibited neurotransmitter relea…
Coordination chemistry of N,N′-bis(coordinating group substituted)oxamides: a rational design of nuclearity tailored polynuclear complexes
1999
Abstract The coordinating properties of N , N ′-bis(coordinating group substituted)oxamides have been thoroughly investigated both in aqueous solution and in the solid state. The easy cis – trans isomerization equilibria that they exhibit together with the great variety of N , N ′-substituents which can be used to play on the overall charge, complexing ability and polarity, make them very suitable ligands in designing homo- and heterometallic species. The knowledge of their complex formation in aqueous solution by potentiometry and using the hydrogen ion concentration as a probe, allowed us to settle the basis of a rational design of oxamidate-containing polynuclear species whose nuclearity…
Analysis of Structure-Activity Relationships of the Bowman-Birk Inhibitor of Serine Proteinases
1993
Proteinase inhibitors are a class of the various dietary inhibitors of mutagenesis and carcinogenesis (Hayatsu et al., 1988). Schelp and Pongpaew (1988) have recently hypothesized that protection against cancer may result from an increase of endogenous proteinase inhibitors such as α2-macroglobulin induced by diets that are low in calories and fat. The Bowman-Birk inhibitor (BBI) of serine proteinases, a double-headed polypeptide-inhibitor of trypsin and chymotrypsin, is one of the most potent cancer chemopreventive agents (Yavelow et al., 1983, 1985). Recently, this property has been substantiated in an in vivo investigation using mice (St. Clair et al., 1990) that were exposed to dimethyl…
Computer-Aided Rational Design of Catalytic Antibodies: The 1F7 Case.
2007
Amphiphilic poly(ether urethanes) carrying associative terpyridine side groups with controlled spacing
2021
The rational design of transiently crosslinked polymer gels requires a profound understanding of how molecular and topological factors determine the mechanical and dynamic material properties. To refine so-far established structure–property relations, complementary and versatile model sytems are still a crucial prerequisiste. In this study, the synthesis of a metallo-supramolecular associating terpyridine-diol (referred to as sticker) and its incorporation into poly(ethylene glycol) (pEG) based polyurethanes (PU) with strictly alternating vs. random sequences and variable sticker spacings is described. Synergetic effects resulting from the proximity of multiple neighboring urethane and stic…
Ligand design for multidimensional magnetic materials: a metallosupramolecular perspective.
2008
The aim and scope of this review is to show the general validity of the ‘complex-as-ligand’ approach for the rational design of metallosupramolecular assemblies of increasing structural and magnetic complexity. This is illustrated herein on the basis of our recent studies on oxamato complexes with transition metal ions looking for the limits of the research avenue opened by Kahn's pioneering research twenty years ago. The use as building blocks of mono-, di- and trinuclear metal complexes with a novel family of aromatic polyoxamato ligands allowed us to move further in the coordination chemistry-based approach to high-nuclearity coordination compounds and high-dimensionality coordination po…
Postsynthetic Approach for the Rational Design of Chiral Ferroelectric Metal–Organic Frameworks
2017
International audience; Ferroelectrics (FEs) are materials of paramount importance with a wide diversity of applications. Herein, we propose a postsynthetic methodology for the smart implementation of ferroelectricity in chiral metal−organic frameworks (MOFs): following a single-crystal to single-crystal cation metathesis, the Ca2+ counterions of a preformed chiral MOF of formula Ca6II{CuII24[(S,S)-hismox]12(OH2)3}·212H2O (1), where hismox is a chiral ligand derived from the natural amino acid l-histidine, are replaced by CH3NH3+. The resulting compound, (CH3NH3)12{CuII24[(S,S)-hismox]12(OH2)3}·178H2O (2), retains the polar space group of 1 and is ferroelectric below 260 K. These results op…