Search results for "pharmacophore"
showing 10 items of 71 documents
A Molecular Dynamics-Shared Pharmacophore Approach to Boost Early-Enrichment Virtual Screening: A Case Study on Peroxisome Proliferator-Activated Rec…
2016
Molecular dynamics (MD) simulations can be used, prior to virtual screening, to add flexibility to proteins and study them in a dynamic way. Furthermore, the use of multiple crystal structures of the same protein containing different co-crystallized ligands can help elucidate the role of the ligand on a protein's active conformation, and then explore the most common interactions between small molecules and the receptor. In this work, we evaluated the contribution of the combined use of MD on crystal structures containing the same protein but different ligands to examine the crucial ligand-protein interactions within the complexes. The study was carried out on peroxisome proliferator-activat…
Pharmacophore study of a blending six-component odor mixture
2016
The first step of odor perception is an interaction between odorants and olfactory receptors [1]. The corresponding transduced olfactory signals, conveyed by olfactory sensory neurons, are then processed by the brain [2]. It is now accepted that the main strategy used to discriminate thousands of odors results from a combinatorial coding [3]. Moreover, odors perceived in our environment are mainly the result of mixtures of odorants; however, the specific mechanisms involved in their processing remain poorly understood [4]. In previous studies performed in the CSGA of Dijon [5-7], we investigated the perception of a mixture of 6 components: vanillin, oxanone (4-(4-hydroxyphenyl)butan-2-one),…
In silico study of correspondences between odors descriptions linked to common features of aromas compounds
2014
The first step of odor detection and discrimination of structurally diverse odorants depends of their interactions with olfactory receptors (ORs) [1], whereas the perception of odors quality results from a combinatorial coding [2], whose identification still remains a major challenge. Recently, Martinez-Mayorga et al. demonstrated that odor description can be successfully analyzed using a metric approach by performing a descriptive analysis of the Flavor Base database (http://www.leffingwell.com, version 2010) [3]. The current version Flavor Base (9th edition, 2013) is one of the largest collections of flavor molecules (4226 molecules). We extracted 3508 molecules for which the described od…
Exploring of odor blending in odorant mixtures by a pharmacophore approach
2015
The first step of odor perception is an interaction between odorants and olfactory receptors (ORs) [1]. It is now accepted that the main strategy used by Humans to perceive thousands of odors results from a combinatorial coding [2]. Moreover, odors we perceived in our environment are mainly the result of mixtures of odorants; however, the processes involved remain poorly understood [3]. In previous studies performed in the CSGA of Dijon[4, 5], the perception of a mixture of specific proportions of ethyl isobutyrate (Et-iB, strawberry-like odor) and ethyl maltol (Et-M, caramel-like odor) was investigated in comparison with a reference (allyl hexanoate, Al-H, pineapple-like odor) chosen to ev…
Exploring the odorant and molecular characteristics of molecules sharing the odour notes of an aroma blending mixture
2021
Online event (Live and on-demand); International audience; To perceive a huge number of odors from few hundreds ORs, the human olfactory system encodes odor identities by an olfactory scheme whereby one olfactory receptor (OR) recognizes multiple odorants while one odorant activates different combinations of ORs [1, 2]. Odors perceived in our environment are mainly the result of mixtures of odorants, but the specific mechanisms involved in their processing remain poorly understood [3]. In previous studies performed at INRAE-CSGA [4], the perception of a mixture of ethyl isobutyrate (Et iB, strawberry-like odor, STR) and ethyl maltol (Et-M, caramel-like odor, CAR) was investigated in compari…
CHA on CDK2: a way to identify the best pharmacophore model for the virtual screening of new inhibitors
2018
Cyclin-dependent kinase-2 (CDK2) is a member of serine/threonine protein kinases family. It plays an important role in the regulation events of the eukaryotic cell division cycle, especially during the G1 to S phase transition. Experimental evidences indicate that excessive expression of CDK2 should cause abnormal cell cycle regulation. Therefore, CDK2 has been considered a potential therapeutic target for cancer therapy. In this work, we used a modelling approach that incorporates flexibility based on extensive MD simulations of protein−ligand complexes into structure-based pharmacophore modeling and virtual screening to identify new CDK2 inhibitors. One-hundred and forty-nine CDK2-inhibit…
A Novel 68Ga-Labeled Pteroic Acid-Based PET Tracer for Tumor Imaging via the Folate Receptor
2012
The folate receptor (FR) is a very attractive target in oncological imaging as it is overexpressed by a variety of cancer types, whereas the expression in healthy tissue is very limited. The synthesis of regioisomeric pure folic acid derivatives normally requires a regioselective approach and does not allow the use of native folic acid (FA). As the pharmacophore of FA is assumed to be pteroic acid, its use without the glutamic acid moiety may enable the possibility to considerably simplify the synthesis of a positron emission tomography (PET) tracer for FR imaging. In this work, DO3A-EA-Pte was successfully synthesized and labeled with 68Ga. It is stable for up to 3 h in PBS and against tra…
A Novel Series of 2-Carboxytetrahydroquinolines Provides New Insights into the Eastern Region of Glycine Site NMDA Antagonists
2000
A series of potent 4-substituted tetrahydroquinolines has been synthesized and biologically tested in order to refine the eastern region of the pharmacophore model for glycine site NMDA antagonists concerning the assessment of lipophilicity, flexibility, and hydrogen bonding. Displacement studies on rat cortical membranes using [ 3 H]-5,7-dichlorokynurenic acid as a radioligand indicated that binding affinities are markedly enhanced when additional hydrogen-accepting groups are introduced into the eastern region of the 2-carboxytetrahydroquinolines. Among the most potent ligands were some urea, sulfonylurea, and crown ether compounds as interesting leads for new diagnostics, especially for …