Synthesis and Preliminary Pharmacological Evaluation of 4′-Arylalkyl Analogues of Clozapine. III. Replacement of the Tricyclic Nucleus with a Bicyclic Template

2007 ◽  
Vol 60 (12) ◽  
pp. 928 ◽  
Author(s):  
Ben Capuano ◽  
Ian T. Crosby ◽  
Edward J. Lloyd ◽  
David A. Taylor
Keyword(s):  
Nitrogen Atom ◽  
Binding Affinity ◽  
Receptor Binding ◽  
Structural Characterization ◽  
Research Program ◽  
Substituent Effects ◽  
Bicyclic Compounds ◽  
Degree Of Unsaturation ◽  
Selection Of

As a continuing part of our research program in search of novel compounds for the treatment of schizophrenia, we report the synthesis and preliminary receptor binding affinity for a series of bicyclic analogues of clozapine derived from a selection of promising tricyclic candidates published previously. These bicyclic compounds investigate some substituent effects and the length and nature of the linker between an ionizable nitrogen atom at physiological pH and the introduced aryl moiety. The chemistry, structural characterization, and in vitro evaluation are described. Preliminary findings on the effects on activity of the nature and length of the linker, degree of unsaturation, and selected substituents coupled to the bicyclic nucleus are discussed in relation to affinity for dopamine D4 and serotonin 5-HT2A receptors.

In Vitro Androgen Receptor Binding Affinity and in Vivo Inhibitory Activity of 5?-Pregnane-3, 20-Dione

1988 ◽  
Vol 529 (1 Fourth Colloq) ◽  
pp. 239-241
Author(s):  
SAUDHAMINI PARTHASARATHY ◽  
ANDREA CHIN ◽  
VIRGINIA MALLOY ◽  
JONATHAN MATIAS
Keyword(s):  
Androgen Receptor ◽  
Binding Affinity ◽  
Receptor Binding ◽  
Inhibitory Activity ◽  
Receptor Binding Affinity

Divergence of the in vitro biological activity and receptor binding affinity of a synthetic insulin analog. [21-Asparaginamide-A]insulin

Biochemistry ◽  
1980 ◽  
Vol 19 (20) ◽  
pp. 4547-4556 ◽  
Author(s):  
G. Thompson Burke ◽  
Jacob D. Chanley ◽  
Yoshio Okada ◽  
Alexandros Cosmatos ◽  
Nicolaos Ferderigos ◽  
...  
Keyword(s):  
Biological Activity ◽  
Binding Affinity ◽  
Receptor Binding ◽  
Insulin Analog ◽  
Receptor Binding Affinity

scholarly journals Effect of identified non-synonymous mutations in DPP4 receptor binding residues among highly exposed human population in Morocco to MERS-CoV through computational approach

PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0258750
Author(s):  
Anass Abbad ◽  
Latifa Anga ◽  
Abdellah Faouzi ◽  
Nadia Iounes ◽  
Jalal Nourlil
Keyword(s):  
Binding Affinity ◽  
Receptor Binding ◽  
Md Simulation ◽  
Structural Changes ◽  
Computational Approach ◽  
Dipeptidyl Peptidase 4 ◽  
Synonymous Mutations ◽  
Binding Residues ◽  
Cellular Entry

Dipeptidyl peptidase 4 (DPP4) has been identified as the main receptor of MERS-CoV facilitating its cellular entry and enhancing its viral replication upon the emergence of this novel coronavirus. DPP4 receptor is highly conserved among many species, but the genetic variability among direct binding residues to MERS-CoV restrained its cellular tropism to humans, camels and bats. The occurrence of natural polymorphisms in human DPP4 binding residues is not well characterized. Therefore, we aimed to assess the presence of potential mutations in DPP4 receptor binding domain (RBD) among a population highly exposed to MERS-CoV in Morocco and predict their effect on DPP4 –MERS-CoV binding affinity through a computational approach. DPP4 synonymous and non-synonymous mutations were identified by sanger sequencing, and their effect were modelled by mutation prediction tools, docking and molecular dynamics (MD) simulation to evaluate structural changes in human DPP4 protein bound to MERS-CoV S1 RBD protein. We identified eight mutations, two synonymous mutations (A291 =, R317 =) and six non-synonymous mutations (N229I, K267E, K267N, T288P, L294V, I295L). Through docking and MD simulation techniques, the chimeric DPP4 –MERS-CoV S1 RBD protein complex models carrying one of the identified non-synonymous mutations sustained a stable binding affinity for the complex that might lead to a robust cellular attachment of MERS-CoV except for the DPP4 N229I mutation. The latter is notable for a loss of binding affinity of DPP4 with MERS-CoV S1 RBD that might affect negatively on cellular entry of the virus. It is important to confirm our molecular modelling prediction with in-vitro studies to acquire a broader overview of the effect of these identified mutations.

scholarly journals Improved Glucose Metabolism In Vitro and In Vivo by an Allosteric Monoclonal Antibody That Increases Insulin Receptor Binding Affinity

PLoS ONE ◽  
2014 ◽  
Vol 9 (2) ◽  
pp. e88684 ◽  
Author(s):  
John A. Corbin ◽  
Vinay Bhaskar ◽  
Ira D. Goldfine ◽  
Daniel H. Bedinger ◽  
Angela Lau ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Glucose Metabolism ◽  
Insulin Receptor ◽  
Binding Affinity ◽  
Receptor Binding ◽  
Receptor Binding Affinity ◽  
Insulin Receptor Binding

Insulin analog possessing higher in vitro biological activity than receptor binding affinity. [21-Proline-B]insulin

Biochemistry ◽  
1983 ◽  
Vol 22 (19) ◽  
pp. 4561-4567 ◽  
Author(s):  
Gerald P. Schwartz ◽  
G. Thompson Burke ◽  
Jacob D. Chanley ◽  
Panayotis G. Katsoyannis
Keyword(s):  
Biological Activity ◽  
Binding Affinity ◽  
Receptor Binding ◽  
Insulin Analog ◽  
Receptor Binding Affinity

scholarly journals Massively Multiplexed Affinity Characterization of Therapeutic Antibodies Against SARS-CoV-2 Variants

2021 ◽  
Author(s):  
Emily Engelhart ◽  
Randolph Lopez ◽  
Ryan Emerson ◽  
Charles Lin ◽  
Colleen Shikany ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Binding Affinity ◽  
Receptor Binding ◽  
Viral Transmission ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Therapeutic Antibodies ◽  
Large Panel

AbstractAntibody therapies represent a valuable tool to reduce COVID-19 deaths and hospitalizations. Multiple antibody candidates have been granted emergency use authorization by the FDA and many more are in clinical trials. Most antibody therapies for COVID-19 are engineered to bind to the receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein and disrupt its interaction with ACE2. Notably, several SARS-CoV-2 strains have accrued mutations throughout the RBD that improve ACE2 binding affinity, enhance viral transmission, and escape some existing antibody therapies. Here, we measure the binding affinity of 33 therapeutic antibodies against a large panel of SARS-CoV-2 variants and related strains of clinical significance to determine epitopic residues, determine which mutations result in loss of binding, and predict how future RBD variants may impact antibody efficacy.One-Sentence SummaryBy measuring protein binding in vitro, we identify which clinical antibodies retain binding to various mutant SARS-CoV-2 strains.

Energetics of ligand-receptor binding affinity on endothelial cells: An in vitro model

2016 ◽  
Vol 144 ◽  
pp. 250-256 ◽  
Author(s):  
Iolanda Fotticchia ◽  
Daniela Guarnieri ◽  
Teresa Fotticchia ◽  
Andrea Patrizia Falanga ◽  
Raffaele Vecchione ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Binding Affinity ◽  
Receptor Binding ◽  
In Vitro Model ◽  
Receptor Binding Affinity ◽  
Vitro Model

scholarly journals 501Y.V2 and 501Y.V3 variants of SARS-CoV-2 lose binding to Bamlanivimab in vitro

2021 ◽  
Author(s):  
Haolin Liu ◽  
Pengcheng Wei ◽  
Qianqian Zhang ◽  
Zhongzhou Chen ◽  
Katja Aviszus ◽  
...  
Keyword(s):  
South Africa ◽  
Binding Affinity ◽  
Receptor Binding ◽  
Binding Domain ◽  
Therapeutic Antibody ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Human Receptor

AbstractWe generated several versions of the receptor binding domain (RBD) of the Spike protein with mutations existing within newly emerging variants from South Africa and Brazil. We found that the mutant RBD with K417N, E484K, and N501Y exchanges has higher binding affinity to the human receptor compared to the wildtype RBD. This mutated version of RBD also completely abolishes the binding to a therapeutic antibody, Bamlanivimab, in vitro.

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