Search results for " libraries"
showing 10 items of 239 documents
Identifying three-way DNA junction-specific small-molecules
2012
Three-way junction DNA (TWJ-DNA, also known as 3WJ-DNA) is an alternative secondary DNA structure comprised of three duplex-DNAs that converge towards a single point, termed the branch point. This point is characterized by unique geometrical properties that make its specific targeting by synthetic small-molecules possible. Such a targeting has already been demonstrated in the solid state but not thoroughly biophysically investigated in solution. Herein, a set of simple biophysical assays has been developed to identify TWJ-specific small-molecule ligands; these assays, inspired by the considerable body of work that has been reported to characterize the interactions between small-molecules an…
Synthesis and Inhibitory Studies of Phosphonic Acid Analogues of Homophenylalanine and Phenylalanine towards Alanyl Aminopeptidases.
2020
A library of novel phosphonic acid analogues of homophenylalanine and phenylalanine, containing fluorine and bromine atoms in the phenyl ring, have been synthesized. Their inhibitory properties against two important alanine aminopeptidases, of human (hAPN, CD13) and porcine (pAPN) origin, were evaluated. Enzymatic studies and comparison with literature data indicated the higher inhibitory potential of the homophenylalanine over phenylalanine derivatives towards both enzymes. Their inhibition constants were in the submicromolar range for hAPN and the micromolar range for pAPN, with 1-amino-3-(3-fluorophenyl) propylphosphonic acid (compound 15c) being one of the best low-molecular inhibitors …
On the Applicability of Elastic Network Normal Modes in Small-Molecule Docking
2012
Incorporating backbone flexibility into protein-ligand docking is still a challenging problem. In protein-protein docking, normal mode analysis (NMA) has become increasingly popular as it can be used to describe the collective motions of a biological system, but the question of whether NMA can also be useful in predicting the conformational changes observed upon small-molecule binding has only been addressed in a few case studies. Here, we describe a large-scale study on the applicability of NMA for protein-ligand docking using 433 apo/holo pairs of the Astex data sets. On the basis of sets of the first normal modes from the apo structure, we first generated for each paired holo structure a…
Design of a bivalent peptide with two independent elements of secondary structure able to fold autonomously.
2008
This article describes a strategy to develop, starting from a de novo design, bivalent peptides containing two different (alpha-helix and beta-hairpin) and independent secondary-structure elements. The design was based on the use of conformationally restricted peptide libraries. Structural characterization by NMR revealed that the peptides were stable and did not show any long-range NOE interactions between the N-terminal beta-hairpin and the C-terminal alpha-helix. These results suggest that the two elements of secondary structure are stable and well folded. Copyright (C) 2008 European Peptide Society and John Wiley & Sons. Ltd.
Sortase A Inhibitors: Recent Advances and Future Perspectives
2015
Here, we describe the most promising small synthetic organic compounds that act as potent Sortase A inhibitors and cater the potential to be developed as antivirulence drugs. Sortase A is a polypeptide of 206 amino acids, which catalyzes two sequential reactions: (i) thioesterification and (ii) transpeptidation. Sortase A is involved in the process of bacterial adhesion by anchoring LPXTG-containing proteins to lipid II. Sortase A inhibitors do not affect bacterial growth, but they restrain the virulence of pathogenic bacterial strains, thereby preventing infections caused by Staphylococcus aureus or other Gram-positive bacteria. The efficacy of the most promising inhibitors needs to be com…
A Primary Evaluation of Potential Small-Molecule Inhibitors of the Astacin Metalloproteinase Ovastacin, a Novel Drug Target in Female Infertility Tre…
2020
Abstract Despite huge progress in hormonal therapy and improved in vitro fertilization methods, the success rates in infertility treatment are still limited. A recently discovered mechanism revealed the interplay between the plasma protein fetuin‐B and the cortical granule‐based proteinase ovastacin to be a novel key mechanism in the regulation of fertilization. Upon sperm–egg fusion, cleavage of a distinct zona pellucida component by ovastacin destroys the sperm receptor, enhances zona robustness, and eventually provides a definitive block against polyspermy. An untimely onset of this zona hardening prior to fertilization would consequently result in infertility. Physiologically, this proc…
Metadata-Oriented Language Model in Translingual Retrieval of Digital Data
2015
Translingual retrieval relies on processing a source language to retrieve digital document content in a target language. From the perspective of successful browsing digital catalogues, probability of retrieving the full text document in a language other than the query language is close to zero owning to the fact that it is not only the library collection, but especially a problem of matching the index terms with the query keywords which are assumed to be their translation equivalents. In addition, hardly any digital library system is incorporated with a translation component. As a result, such a matching is rather coincidental. Our approach to the translingual document retrieval problem is …
Small molecule inhibitors of Apaf-1-related caspase- 3/-9 activation that control mitochondrial-dependent apoptosis
2006
10 pages, 5 figures.-- PMID: 16341125 [PubMed].-- Available online Dec 9, 2005.
Dynamics of ionized and neutral gas in M8
2017
We present a spectroscopic study of the dynamics of the ionized and neutral gas throughout the Lagoon nebula (M8), using VLT/FLAMES data from the Gaia-ESO Survey. We explore the connections between the nebular gas and the stellar population of the associated star cluster NGC6530. We characterize through spectral fitting emission lines of H{alpha}, [NII] and [SII] doublets, [OIII], and absorption lines of sodium D doublet, using data from the FLAMES/Giraffe and UVES spectrographs, on more than 1000 sightlines towards the entire face of the Lagoon nebula. Gas temperatures are derived from line-width comparisons, densities from the [SII] doublet ratio, and ionization parameter from H{alpha}/[N…
Leading order corrections to the Bethe-Heitler process in the γp→l+l−p reaction
2019
The ratio of dilepton production cross sections on a proton, using the γp→l+l−p process, above and below the dimuon production threshold allows one to extract the effective lepton-proton interaction, which is required to be identical for electrons and muons if lepton universality is exact. To test for a scenario of broken universality at the percent level, of the size that could explain the different proton charge radii extracted from electron scattering and from muonic hydrogen spectroscopy, we evaluate all one-loop QED corrections to this process, including the full lepton mass dependencies. We furthermore show that two photon–exchange processes with both photons attached to the proton li…