Design, Synthesis, and Binding Studies of New Potent Ligands of Cannabinoid Receptors

2005 ◽  
Vol 48 (23) ◽  
pp. 7343-7350 ◽  
Author(s):  
Antonella Brizzi ◽  
Vittorio Brizzi ◽  
Maria Grazia Cascio ◽  
Tiziana Bisogno ◽  
Rossella Sirianni ◽  
...  
Keyword(s):  
Cannabinoid Receptors ◽  
Binding Studies ◽  
Design Synthesis

scholarly journals CB2 cannabinoid receptor agonist enantiomers HU-433 and HU-308: An inverse relationship between binding affinity and biological potency

2015 ◽  
Vol 112 (28) ◽  
pp. 8774-8779 ◽  
Author(s):  
Reem Smoum ◽  
Saja Baraghithy ◽  
Mukesh Chourasia ◽  
Aviva Breuer ◽  
Naama Mussai ◽  
...  
Keyword(s):  
Bone Loss ◽  
Binding Affinity ◽  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Osteoclast Differentiation ◽  
Protective Mechanism ◽  
Binding Studies ◽  
Age Related ◽  
Comparative Binding ◽  
Biological Potency

Activation of the CB2 receptor is apparently an endogenous protective mechanism. Thus, it restrains inflammation and protects the skeleton against age-related bone loss. However, the endogenous cannabinoids, as well as Δ9-tetrahydrocannabinol, the main plant psychoactive constituent, activate both cannabinoid receptors, CB1 and CB2. HU-308 was among the first synthetic, selective CB2 agonists. HU-308 is antiosteoporotic and antiinflammatory. Here we show that the HU-308 enantiomer, designated HU-433, is 3–4 orders of magnitude more potent in osteoblast proliferation and osteoclast differentiation culture systems, as well as in mouse models, for the rescue of ovariectomy-induced bone loss and ear inflammation. HU-433 retains the HU-308 specificity for CB2, as shown by its failure to bind to the CB1 cannabinoid receptor, and has no activity in CB2-deficient cells and animals. Surprisingly, the CB2 binding affinity of HU-433 in terms of [3H]CP55,940 displacement and its effect on [35S]GTPγS accumulation is substantially lower compared with HU-308. A molecular-modeling analysis suggests that HU-433 and -308 have two different binding conformations within CB2, with one of them possibly responsible for the affinity difference, involving [35S]GTPγS and cAMP synthesis. Hence, different ligands may have different orientations relative to the same binding site. This situation questions the usefulness of universal radioligands for comparative binding studies. Moreover, orientation-targeted ligands have promising potential for the pharmacological activation of distinct processes.

Design, Synthesis, Photophysics, and Anion-Binding Studies of Bis(dicyclohexylphosphino)methane-Containing Dinuclear Gold(I) Thiolate Complexes with Urea Receptors

2010 ◽  
Vol 16 (30) ◽  
pp. 9123-9131 ◽  
Author(s):  
Xiaoming He ◽  
Fernando Herranz ◽  
Eddie Chung-Chin Cheng ◽  
Ramon Vilar ◽  
Vivian Wing-Wah Yam
Keyword(s):  
Anion Binding ◽  
Binding Studies ◽  
Design Synthesis ◽  
Thiolate Complexes

Design, synthesis and binding studies of a novel quadruple ADDA hydrogen-bond array

2012 ◽  
Vol 10 (25) ◽  
pp. 4899 ◽  
Author(s):  
Maria L. Pellizzaro ◽  
Simon A. Barrett ◽  
Julie Fisher ◽  
Andrew J. Wilson
Keyword(s):  
Hydrogen Bond ◽  
Binding Studies ◽  
Design Synthesis

scholarly journals Synthesis and binding studies of two new macrocyclic receptors for the stereoselective recognition of dipeptides

2010 ◽  
Vol 6 ◽  
Author(s):  
Ana Maria Castilla ◽  
M Morgan Conn ◽  
Pablo Ballester
Keyword(s):  
Hydrogen Bonding ◽  
Peptide Ligands ◽  
Binding Studies ◽  
Design Synthesis ◽  
Macrocyclic Receptors ◽  
H Nmr ◽  
Hydrogen Bonding Pattern ◽  
Conformational Equilibria ◽  
Β Sheets ◽  
Β Sheet

We present here the design, synthesis, and analysis of a series of receptors for peptide ligands inspired by the hydrogen-bonding pattern of protein β-sheets. The receptors themselves can be regarded as strands 1 and 3 of a three-stranded β-sheet, with cross-linking between the chains through the 4-position of adjacent phenylalanine residues. We also report on the conformational equilibria of these receptors in solution as well as on their tendency to dimerize. 1H NMR titration experiments are used to quantify the dimerization constants, as well as the association constant values of the 1:1 complexes formed between the receptors and a series of diamides and dipeptides. The receptors show moderate levels of selectivity in the molecular recognition of the hydrogen-bonding pattern present in the diamide series, selecting the α-amino acid-related hydrogen-bonding functionality. Only one of the two cyclic receptors shows modest signs of enantioselectivity and moderate diastereoselectivity in the recognition of the enantiomers and diastereoisomers of the Ala-Ala dipeptide (ΔΔG 0 1 (DD-DL) = −1.08 kcal/mol and ΔΔG 0 1 (DD-LD) = −0.89 kcal/mol). Surprisingly, the linear synthetic precursors show higher levels of stereoselectivity than their cyclic counterparts.

scholarly journals Design, synthesis, and pharmacology of some oxadiazole and hydroxypyrazoline hybrids bearing thiazoyl scaffold: antiproliferative activity, molecular docking and DNA binding studies

Heliyon ◽  
2019 ◽  
Vol 5 (2) ◽  
pp. e01255 ◽  
Author(s):  
Rangappa Santosh ◽  
Ashwini Prabhu ◽  
Mukunthan K. Selvam ◽  
Panchangam M. Krishna ◽  
Gundibasappa K. Nagaraja ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Dna Binding ◽  
Antiproliferative Activity ◽  
Binding Studies ◽  
Design Synthesis ◽  
Dna Binding Studies

Design, synthesis and exploration of in silico α-amylase and α-glucosidase binding studies of pyrrolidine-appended quinoline-constrained compounds

2020 ◽  
Vol 46 (3) ◽  
pp. 1869-1880
Author(s):  
P. Hemanth Kumar ◽  
L. Jyothish Kumar ◽  
G. Pavithrra ◽  
R. Rajasekaran ◽  
V. Vijayakumar ◽  
...  
Keyword(s):  
In Silico ◽  
Binding Studies ◽  
Design Synthesis
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