PMID: 11342390May 9, 2001Paper

Possible influence of intramolecular hydrogen bonds on the three-dimensional structure of polyamine amides and their interaction with ionotropic glutamate receptors

Receptors & Channels
D B TikhonovP N Usherwood

Abstract

Polyamine amides are potent antagonists of many classes of ionotropic receptor. Here, calculations of the conformations of 26 polyamine amides using molecular mechanics methodology have shown that intramolecular hydrogen bonds strongly influence the in vacuo three-dimensional structure of a polyamine amide. Although these bonds are less stable in an aqueous environment, they may occur more when a polyamine amide interacts with a binding site. The estimated three-dimensional structures of polyamine amides provide an explanation for the differences in their antagonist potency at quisqualate-sensitive ionotropic glutamate receptors (qGluR) observed in experimental studies. Relative antagonist potency at qGluR is correlated with the number of free amino groups on a polyamine amide, i.e. those not involved in intramolecular hydrogen bonds. Also, intramolecular hydrogen bonds significantly restrict the conformational freedom of the uncharged moiety of a polyamine amide. Docking of polyamine amides to a molecular model of a mammalian AMPA receptor (GluR1) channel shows that intramolecular H-bonds may also provide a good structural explanation for the action of these compounds at this site.

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.