Development of Approaches to Reducing the Effective Gonadotropin Dose in Treating Androgen Insufficiency in Male Rats with Type 1 Diabetes Mellitus

Bakhtyukov, A. A.; Morina, I. Yu.; Derkach, K. V.; Романова, И. В.; Sorokoumov, V. N.; Шпаков, А. О.

doi:10.1134/s0022093022050209

Cited by 4 publications

(2 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Using molecular docking, it was found that the efficiency and selectivity of the studied thieno[2,3-d]-pyrimidines correlate with the characteristics of their binding to the transmembrane allosteric site of LHR, and the key parameter of such binding was the intensity of hydrophobic contact while the Coulomb interactions and hydrogen bonds were less significant [ 400 ]. When co-administered with low doses of gonadotropin, thieno[2,3-d]-pyrimidines potentiated its effect, and potentiation was more pronounced in rats with type 1 diabetes mellitus [ 405 ]. As with hCG, TP03 and TP04 improved spermatogenesis in diabetic and aging rats [ 400 , 402 , 406 , 407 ].…”

Section: Allosteric Regulators Of Pituitary Glycoprotein Hormone Rece...mentioning

confidence: 99%

Allosteric Regulation of G-Protein-Coupled Receptors: From Diversity of Molecular Mechanisms to Multiple Allosteric Sites and Their Ligands

2023

IJMS

View full text Add to dashboard Cite

Allosteric regulation is critical for the functioning of G protein-coupled receptors (GPCRs) and their signaling pathways. Endogenous allosteric regulators of GPCRs are simple ions, various biomolecules, and protein components of GPCR signaling (G proteins and β-arrestins). The stability and functional activity of GPCR complexes is also due to multicenter allosteric interactions between protomers. The complexity of allosteric effects caused by numerous regulators differing in structure, availability, and mechanisms of action predetermines the multiplicity and different topology of allosteric sites in GPCRs. These sites can be localized in extracellular loops; inside the transmembrane tunnel and in its upper and lower vestibules; in cytoplasmic loops; and on the outer, membrane-contacting surface of the transmembrane domain. They are involved in the regulation of basal and orthosteric agonist-stimulated receptor activity, biased agonism, GPCR-complex formation, and endocytosis. They are targets for a large number of synthetic allosteric regulators and modulators, including those constructed using molecular docking. The review is devoted to the principles and mechanisms of GPCRs allosteric regulation, the multiplicity of allosteric sites and their topology, and the endogenous and synthetic allosteric regulators, including autoantibodies and pepducins. The allosteric regulation of chemokine receptors, proteinase-activated receptors, thyroid-stimulating and luteinizing hormone receptors, and beta-adrenergic receptors are described in more detail.

show abstract

Section: Allosteric Regulators Of Pituitary Glycoprotein Hormone Rece...mentioning

confidence: 99%

Allosteric Regulation of G-Protein-Coupled Receptors: From Diversity of Molecular Mechanisms to Multiple Allosteric Sites and Their Ligands

2023

IJMS

View full text Add to dashboard Cite

show abstract

“…We have developed a series of thieno [2,3-d the key parameter of such binding was the intensity of hydrophobic contact, while the Coulomb interactions and hydrogen bonds were less significant [400]. When coadministered with low doses of gonadotropin, thieno [2,3-d]-pyrimidines potentiated its effect, and potentiation was more pronounced in rats with type 1 diabetes mellitus [405].…”

Section: Luteinizing Hormone Receptormentioning

confidence: 99%

Allosteric Regulation of G-Protein-Coupled Receptors: From Diversity of Molecular Mechanisms to Multiple Allosteric Sites and Their Ligands

Ao¹

2023

Preprint

View full text Add to dashboard Cite

A separate group consists of compounds that are able to simultaneously interact with both orthosteric and allosteric sites, which are classified as bitopic GPCR ligands [74, 76-81]. They have two pharmacophores, one of which binds with high affinity to the orthosteric site, while the other, with lower affinity, binds to the allosteric site. If these sites are spatially separated in the receptor, then the pharmacophores in the bitopic ligand must be connected with a flexible linker, the length of which exactly corresponds to the distance between the orthosteric and allosteric sites. At the same time, it is important that the linker does not significantly affect the conformational rearrangements in the receptor caused by its activation by orthosteric and (or) allosteric agonists [74, 79].

show abstract

Allosteric Sites and Allosteric Regulators of G Protein-Coupled Receptors: Gray Cardinals of Signal Transduction

Shpakov

2023

J Evol Biochem Phys

View full text Add to dashboard Cite

Development of Approaches to Reducing the Effective Gonadotropin Dose in Treating Androgen Insufficiency in Male Rats with Type 1 Diabetes Mellitus

Cited by 4 publications

References 22 publications

Allosteric Regulation of G-Protein-Coupled Receptors: From Diversity of Molecular Mechanisms to Multiple Allosteric Sites and Their Ligands

Allosteric Regulation of G-Protein-Coupled Receptors: From Diversity of Molecular Mechanisms to Multiple Allosteric Sites and Their Ligands

Allosteric Regulation of G-Protein-Coupled Receptors: From Diversity of Molecular Mechanisms to Multiple Allosteric Sites and Their Ligands

Allosteric Sites and Allosteric Regulators of G Protein-Coupled Receptors: Gray Cardinals of Signal Transduction

Contact Info

Product

Resources

About