Biologically Relevant Applications of Vibrational Circular Dichroism
R. Michael Gendreau in Spectroscopy in the Biomedical Sciences, 1986
We have also studied transition metal complexes in the NH stretching region in acidic D2O solutions.14 The low pD conditions prevent the exchange of the nitrogen hydrogens in the tris Co(III) complexes of alanine. This molecule exhibits three forms of chirality: (1) configurational by virtue of the sense of the propeller form by the three bidentate amino acid ligands; (2) vicinal by the absolute configuration of the constituent amino acids and; (3) conformational through the stereo-geometry of the amino acid backbone and side chains. In the N-H stretching region of the amino groups of alanine ligated to Co(III), the configurational chirality is the dominant effect whereas in the C-H stretching region, the vicinal effect appears to be the most important.
Radiotracer Interactions with Sex Steroid Hormone Receptor Proteins (Receptor Mapping)
Lelio G. Colombetti in Principles of Radiopharmacology, 1979
The overall picture of the interaction between an estrogen and the active site on the receptor protein molecule is a complicated and still poorly understood one. In addition to the structure-activity relationships listed already for steroidal estrogens, subsequent discussions have also contributed to the following generalized structure-activity relationships: Two polar hydroxyl groups, separated by the appropriate distance and with one attached to an aromatic ring are required for high binding affinity.The molecule must have structural “thickness” in the hydrophobic region for high affinity.The molecule must have the appropriate chirality or “twistedness” — or have the ability to twist to have high receptor binding affinity.
Chemical Causes of Cancer
Peter G. Shields in Cancer Risk Assessment, 2005
The biotransformation enzymes described above, while often having broad substrate specificity, can show remarkable specificity in the chirality of products formed; for example, in biotransformation of B[a]P, the dihy-drodiols are always trans, whereas one of the four possible isomers of B[a]P diolepoxide (BPDE), the R, S-dihydrodiol S, R-epoxide, is formed predominately and also reacts with DNA preferentially (272). No proteins have been described which specifically assist in the binding of the ultimate carcinogens to DNA, although the structure of chromatin is important (273) and numerous enzyme systems are involved in repair of such damage (see below). Consequently, shortly after exposure to DNA-reactive carcinogens, patterns of DNA adducts formed in vivo and in vitro are generally similar.
Tinnitus: still ‘A Ghost in the Machine’ or a Darwinian survival phenomenon?
Published in International Journal of Neuroscience, 2018
Quantum teleportation (tunnelling) involves the ability of an electron to transport from one position to another without evidence of traversing the intervening space. This is only possible in quantum physics (due to the plausibility of another dimension which is not amenable to our current measurement techniques). This allows chirality which is the ability of a chemical substance to assume ‘form stereotaxis’ (folding) within the same molecular formula. To be stable, the form must possess the lowest energy minima. Such quantum chirality effects also occur in very negligible (instantaneous) time. Such effects open up shortcuts to many different, otherwise inaccessible states and such availability of low-energy states is taken advantage of and routinized by biological evolution (cf. enzyme-mediated catalysis [48]).
A patent review of adenosine A2B receptor antagonists (2016-present)
Published in Expert Opinion on Therapeutic Patents, 2022
Beatrice Francucci, Diego Dal Ben, Catia Lambertucci, Andrea Spinaci, Rosaria Volpini, Gabriella Marucci, Michela Buccioni
Forty-three pyridone derivatives able to modulate the A2A/A2BARs were patented in 2020 [115]. The compounds of this invention were tested in CHO cells stable transfected with adenosine receptors and their KB on A2A and A2BARs were obtained through the quantification of intracellular cAMP. All of them have a high affinity toward A2AAR, while as regards A2BR this parameter varies according to the substituents present in the central nucleus. Chirality of the carbon is also important for the activity. The stereoisomer 1-[(R)-1-(2-hydroxy-2-methylpropionyl)-3-pyrrolidinyl]-3-{[4-(2-amino-8-methoxy-4-quinazolinyl)-1 H-1,2,3-triazol-1-yl]methyl}-1 H-pyridin-2-one is more affine than to its enantiomer especially vs A2BAR.
An updated patent review of autotaxin inhibitors (2017–present)
Published in Expert Opinion on Therapeutic Patents, 2021
Zehui Tan, Hongrui Lei, Ming Guo, Yuxiang Chen, Xin Zhai
Mitsubishi Tanabe Pharma Corporation has claimed a class of 2-aminopyrimidine derivatives in 2015 which has been reported in a previous review [15,80]. Starting from 2-aminopyrimidines, the same company developed a range of novel ATX inhibitors bearing pyridazine and pyridine scaffold by bioisosterism strategies [81]. Pyridazine analog 24 presented in vitro human ATX inhibitory activity with IC50 value of 1 nM (LPC assay) and significantly inhibited ex vivo plasma ATX activity by 91% at a dose of 1.0 mg/kg oral administered to Wistar rat. Of note, the replacement of pyridazine scaffold with pyridine leads to a slightly decrease in potency, pyridine analog 25 inhibited the enzyme with an IC50 value of 5 nM (LPC assay) and plasma ATX activity by 82%, suggesting that pyridazine scaffold is beneficial for activity. Furthermore, chirality seems to be less important for these molecules for that the (S, S)-enantiomers on cyclopropane is slightly higher than (R, R)-enantiomers in potency. In addition, Inhibitaxin Limited covered several pyridazine analogs in the patent, as well[82]. Typically, 26 exerted ATX inhibition with an IC50 value of 14.0 nM in the FS-3 assay.
Related Knowledge Centers
- Chirality
- Circular Dichroism
- Enantiomer
- Hand
- Molecule
- Mirror Image
- Point Group
- Optical Rotation
- Planar Chirality
- Asymmetric Carbon