Search results for "Models"
showing 10 items of 8211 documents
Monoclonal antibody to a DNA-binding domain of p53 mimics charge structure of DNA: anti-idiotypes to the anti-p53 antibody are anti-DNA
2004
Antibodies to DNA are important markers of various autoimmune diseases and can be pathogenic; however, their generation is not understood. We previously reported that anti-DNA antibodies could be induced in mice by idiotypic immunization to PAb-421, an antibody to a DNA-binding domain of p53. We now report that two monoclonal antibodies of moderate affinity (K(D) asymptotically equal to 10(-7)), raised from PAb-421-immunized mice, specifically recognized both PAb-421 and DNA. These antibodies feature multiple arginine residues in the antigen-binding site, a unique characteristic of disease-associated anti-DNA antibodies; nevertheless, these anti-DNA antibodies show specific complementarity …
Virtual Combinatorial Syntheses and Computational Screening of New Potential Anti-Herpes Compounds
1999
The activity of new anti-HSV-1 chemical structures, designed by virtual combinatorial chemical synthesis and selected by a computational screening, is determined by an in vitro assay. A virtual library of phenol esters and anilides was formed from two databases of building blocks: one with carbonyl fragments and the other containing both substituted phenoxy and phenylamino fragments. The library of virtually assembled compounds was computationally screened, and those compounds which were selected by our mathematical model as active ones were finally synthesized and tested. Our antiviral activity model is a "tandem" of four linear functions of topological graph-theoretical descriptors. A giv…
Leucine-58 in the putative 5th helical region of human interleukin (IL)-6 is important for activation of the IL-6 signal transducer, gp130
1995
A model of the tertiary structure of human IL-6, derived from the crystal-structure of granulocyte-colony stimulating factor, reveals a 5th helical region in the loop between the first and second alpha-helix. To investigate the importance of this region for biological activity of IL-6, residues Glu-52, Ser-53, Ser-54, Lys-55, Glu-56, Leu-58, and Glu-60 were individually replaced by alanine. IL-6.Leu-58Ala displayed a 5-fold reduced biological activity on the IL-6 responsive human cell lines XG-1 and A375. This reduction in bioactivity was shown to be due to a decreased capacity of the mutant protein to trigger IL-6 receptor-alpha-chain-dependent binding to the IL-6 signal transducer, gp130.
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…
The family of the IL-6-type cytokines: specificity and promiscuity of the receptor complexes.
1997
The cytokines IL-6, LIF, CNTF, OSM, IL-11, and CT-1 have been grouped into the family of IL-6-type cytokines, since they all require gp130 for signal transduction. Interestingly, gp130 binds directly to OSM, whereas complex formation with the other cytokines depends on additional receptor subunits. Only limited structural information on these cytokines and their receptors is available. X-ray structures have been solved for the cytokines LIF and CNTF, whose up-up-down-down four-helix bundle is common to all of these cytokines, and for the receptors of hGH and prolactin, which contain two domains with a fibronectin III-like fold. Since cocrystallization and x-ray analysis of the up to four di…
Multiple Decay Mechanisms and 2D-UV Spectroscopic Fingerprints of Singlet Excited Solvated Adenine-Uracil Monophosphate
2016
The decay channels of singlet excited adenine uracil monophosphate (ApU) in water are studied with CASPT2//CASSCF:MM potential energy calculations and simulation of the 2D-UV spectroscopic fingerprints with the aim of elucidating the role of the different electronic states of the stacked conformer in the excited state dynamics. The adenine 1La state can decay without a barrier to a conical intersection with the ground state. In contrast, the adenine 1Lb and uracil S(U) states have minima that are separated from the intersections by sizeable barriers. Depending on the backbone conformation, the CT state can undergo inter-base hydrogen transfer and decay to the ground state through a conical …
Reaction of 3-Amino-1,2,4-Triazole with Diethyl Phosphite and Triethyl Orthoformate: Acid-Base Properties and Antiosteoporotic Activities of the Prod…
2017
The reaction of diethyl phosphite with triethyl orthoformate and a primary amine followed by hydrolysis is presented, and the reaction was suitable for the preparation of (aminomethylene)bisphosphonates. 3-Amino-1,2,4-triazole was chosen as an interesting substrate for this reaction because it possesses multiple groups that can serve as the amino component in the reaction-namely, the side-chain and triazole amines. This substrate readily forms 1,2,4-triazolyl-3-yl-aminomethylenebisphosphonic acid (compound 1) as a major product, along with N-ethylated bisphosphonates as side products. The in vitro antiproliferative effects of the synthesized aminomethylenebisphosphonic acids against J774E m…
The Low Barrier Hydrogen Bond in the Photoactive Yellow Protein: A Vacuum Artifact Absent in the Crystal and Solution
2016
Journal of the American Chemical Society 138(51), 16620 - 16631 (2016). doi:10.1021/jacs.6b05609
Toward engineering efficient peptidomimetics. Screening conformational landscape of two modified dehydroaminoacids
2013
Effective peptidomimetics should posses structural rigidity and appropriate interaction pattern leading to potential spatial and electronic matching to the target receptor site. Rational design of such small bioactive molecules could push chemical synthesis and molecular modeling toward faster progress in medicinal chemistry. Conformational properties of N-t-butoxycarbonyl-glycine-(E/Z)-dehydrophenylalanine N′,N′-dimethylamides (Boc-Gly-(E/Z)-ΔPhe-NMe2) in chloroform were studied by NMR and IR spectroscopy. The experimental findings were supported by extensive calculations at DFT(B3LYP, M06-2X) and MP2 levels of theory and the β-turn tendency for both isomers of the studied dipeptide were d…
Dynamical Properties of Self-Assembled Surfactant-Based Mixtures: Triggering of One-Dimensional Anomalous Diffusion in Bis(2-ethylhexyl)phosphoric Ac…
2013
The dynamic features of bis(2-ethylhexyl)phosphoric acid (HDEHP)/n-octylamine (NOA) mixtures have been investigated as a function of the NOA mole fraction and temperature by (1)H NMR spectroscopy and rheometry. All data consistently suggest a composition-induced glass-forming behavior. The microscopic factors responsible for this behavior have been highlighted and have been explained in terms of driving forces given by HDEHP-to-NOA proton transfer, the tendency of the resulting species to establish H bonds and to spatially segregate the alkyl chains. The study sheds light on the molecular mechanism responsible for the peculiar behavior of transport properties in such systems and furnishes b…