Hexadimethrine bromide

Last updated
Hexadimethrine bromide
Polybrene with bromide.svg
Names
IUPAC name
1,5-Dimethyl-1,5-diazaundecamethylene polymethobromide
Other names
Polybrene
Identifiers
  • 28728-55-4 Yes check.svgY
ChemSpider
  • none
ECHA InfoCard 100.209.698 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 684-236-5
UNII
Properties
(C13H30Br2N2)n, linear form
Molar mass variable
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

Hexadimethrine bromide (commercial brand name Polybrene) is a cationic polymer with several uses. Currently, it is primarily used to increase the efficiency of transduction of certain cells with retrovirus in cell culture. [1] Hexadimethrine bromide acts by neutralizing the charge repulsion between virions and sialic acid on the cell surface. [2] Use of Polybrene can improve transduction efficiency 100-1000 fold [3] although it can be toxic to some cell types. Polybrene in combination with DMSO shock is used to transfect some cell types such as NIH-3T3 and CHO. [3] It has other uses, including a role in protein sequencing. [4]

Hexadimethrine bromide also reverses heparin anticoagulation during open-heart surgery, and it was the original reversal agents used in the 1950s and 1960s. [5] It was replaced by protamine sulfate in 1969, after it was shown that hexadimethrine bromide could potentially cause kidney failure in dogs when used in doses in excess of its therapeutic range. [6] It is still used as an alternative to protamine sulfate for patients who are sensitive to protamine, and at least one surgical center has gone back to using it as their standard reversal agent, since protamine sulfate causes at least a mild hypotensive reaction in most or all patients [5]

Hexadimethrine bromide is also used in enzyme kinetic assays in order to reduce spontaneous activation of zymogens that are prone to auto activation.[ citation needed ]

Related Research Articles

Retrovirus Family of viruses

A retrovirus is a type of virus that inserts a copy of its RNA genome into the DNA of a host cell that it invades, thus changing the genome of that cell. Once inside the host cell's cytoplasm, the virus uses its own reverse transcriptase enzyme to produce DNA from its RNA genome, the reverse of the usual pattern, thus retro (backwards). The new DNA is then incorporated into the host cell genome by an integrase enzyme, at which point the retroviral DNA is referred to as a provirus. The host cell then treats the viral DNA as part of its own genome, transcribing and translating the viral genes along with the cell's own genes, producing the proteins required to assemble new copies of the virus.

Heparin Anticoagulant

Heparin, also known as unfractionated heparin (UFH), is a medication and naturally occurring glycosaminoglycan. Since heparins depend on the activity of AT, they are considered anticoagulants. Specifically it is also used in the treatment of heart attacks and unstable angina. It is given by injection into a vein or under the skin. Other uses include inside test tubes and kidney dialysis machines.

Cardiopulmonary bypass Technique that temporarily takes over the function of the heart and lungs during surgery

Cardiopulmonary bypass (CPB) is a technique in which a machine temporarily takes over the function of the heart and lungs during surgery, maintaining the circulation of blood and the oxygen content of the patient's body. The CPB pump itself is often referred to as a heart–lung machine or "the pump". Cardiopulmonary bypass pumps are operated by perfusionists. CPB is a form of extracorporeal circulation. Extracorporeal membrane oxygenation is generally used for longer-term treatment.

Low-molecular-weight heparin (LMWH) is a class of anticoagulant medications. They are used in the prevention of blood clots and treatment of venous thromboembolism and in the treatment of myocardial infarction.

Transfection is the process of deliberately introducing naked or purified nucleic acids into eukaryotic cells. It may also refer to other methods and cell types, although other terms are often preferred: "transformation" is typically used to describe non-viral DNA transfer in bacteria and non-animal eukaryotic cells, including plant cells. In animal cells, transfection is the preferred term as transformation is also used to refer to progression to a cancerous state (carcinogenesis) in these cells. Transduction is often used to describe virus-mediated gene transfer into eukaryotic cells.

Transduction (genetics) Transfer of genetic information to a bacterium from a bacteriophage or between bacterial or yeast cells mediated by a phage vector

Transduction is the process by which foreign DNA is introduced into a cell by a virus or viral vector. An example is the viral transfer of DNA from one bacterium to another and hence an example of horizontal gene transfer. Transduction does not require physical contact between the cell donating the DNA and the cell receiving the DNA, and it is DNase resistant. Transduction is a common tool used by molecular biologists to stably introduce a foreign gene into a host cell's genome.

Lipid raft

The plasma membranes of cells contain combinations of glycosphingolipids, cholesterol and protein receptors organised in glycolipoprotein lipid microdomains termed lipid rafts. Their existence in cellular membranes remains somewhat controversial. It has been proposed that they are specialized membrane microdomains which compartmentalize cellular processes by serving as organising centers for the assembly of signaling molecules, allowing a closer interaction of protein receptors and their effectors to promote kinetically favorable interactions necessary for the signal transduction. Lipid rafts influence membrane fluidity and membrane protein trafficking, thereby regulating neurotransmission and receptor trafficking. Lipid rafts are more ordered and tightly packed than the surrounding bilayer, but float freely within the membrane bilayer. Although more common in the cell membrane, lipid rafts have also been reported in other parts of the cell, such as the Golgi apparatus and lysosomes.

Glycosaminoglycan Polysaccharides found in animal tissue

Glycosaminoglycans (GAGs) or mucopolysaccharides are long linear polysaccharides consisting of repeating disaccharide units. The repeating two-sugar unit consists of a uronic sugar and an amino sugar, with the exception of keratan, where in the place of the uronic sugar it has galactose. Because GAGs are highly polar and attract water, they are used in the body as a lubricant or shock absorber. Mucopolysaccharidoses are a group of metabolic disorders in which abnormal accumulations of glycosaminoglycans occur because of enzyme deficiencies.

Protamine sulfate is a medication that is used to reverse the effects of heparin. It is specifically used in heparin overdose, in low molecular weight heparin overdose, and to reverse the effects of heparin during delivery and heart surgery. It is given by injection into a vein. The onset of effects is typically within five minutes.

Protamines are small, arginine-rich, nuclear proteins that replace histones late in the haploid phase of spermatogenesis and are believed essential for sperm head condensation and DNA stabilization. They may allow for denser packaging of DNA in the spermatozoon than histones, but they must be decompressed before the genetic data can be used for protein synthesis. However, in humans and maybe other primates, 10-15% of the sperm's genome is packaged by histones thought to bind genes that are essential for early embryonic development.

Basic fibroblast growth factor Growth factor and signaling protein otherwise known as FGF2

FGF2, also known as basic fibroblast growth factor (bFGF) and FGF-β, is a growth factor and signaling protein encoded by the FGF2 gene. It binds to and exerts effects via specific fibroblast growth factor receptor (FGFR) proteins, themselves a family of closely related molecules. Fibroblast growth factor protein was first purified in 1975; soon thereafter three variants were isolated: 'basic FGF' (FGF2); Heparin-binding growth factor-2; and Endothelial cell growth factor-2. Gene sequencing revealed that this group is the same FGF2 protein and is a member of a family of FGF proteins.

Envelope glycoprotein GP120 Glycoprotein exposed on the surface of the HIV virus

Envelope glycoprotein GP120 is a glycoprotein exposed on the surface of the HIV envelope. It was discovered by Professors Tun-Hou Lee and Myron "Max" Essex of the Harvard School of Public Health in 1988. The 120 in its name comes from its molecular weight of 120 kDa. Gp120 is essential for virus entry into cells as it plays a vital role in attachment to specific cell surface receptors. These receptors are DC-SIGN, Heparan Sulfate Proteoglycan and a specific interaction with the CD4 receptor, particularly on helper T-cells. Binding to CD4 induces the start of a cascade of conformational changes in gp120 and gp41 that lead to the fusion of the viral membrane with the host cell membrane. Binding to CD4 is mainly electrostatic although there are van der Waals interactions and hydrogen bonds.

P-selectin Type-1 transmembrane protein

P-selectin is a type-1 transmembrane protein that in humans is encoded by the SELP gene.

FGF1

FGF1, also known as acidic fibroblast growth factor (aFGF), is a growth factor and signaling protein encoded by the FGF1 gene. It is synthesized as a 155 amino acid polypeptide, whose mature form is a non-glycosylated 17-18 kDa protein. Fibroblast growth factor protein was first purified in 1975, but soon afterwards others using different conditions isolated acidic FGF, Heparin-binding growth factor-1, and Endothelial cell growth factor-1. Gene sequencing revealed that this group was actually the same growth factor and that FGF1 was a member of a family of FGF proteins.

Heparan sulfate Linear polysaccharide in all animal tissues

Heparan sulfate (HS) is a linear polysaccharide found in all animal tissues. It occurs as a proteoglycan in which two or three HS chains are attached in close proximity to cell surface or extracellular matrix proteins. It is in this form that HS binds to a variety of protein ligands, including Wnt, and regulates a wide range of biological activities, including developmental processes, angiogenesis, blood coagulation, abolishing detachment activity by GrB, and tumour metastasis. HS has also been shown to serve as cellular receptor for a number of viruses, including the respiratory syncytial virus. One study suggests that cellular heparan sulfate has a role in SARS-CoV-2 Infection, particularly when the virus attaches with ACE2.

Oxygenator

An oxygenator is a medical device that is capable of exchanging oxygen and carbon dioxide in the blood of human patient during surgical procedures that may necessitate the interruption or cessation of blood flow in the body, a critical organ or great blood vessel. These organs can be the heart, lungs or liver, while the great vessels can be the aorta, pulmonary artery, pulmonary veins or vena cava.

In enzymology, a polyphosphate kinase, or polyphosphate polymerase, is an enzyme that catalyzes the formation of polyphosphate from ATP, with chain lengths of up to a thousand or more orthophosphate moieties.

Tat (HIV)

In molecular biology, Tat is a protein that is encoded for by the tat gene in HIV-1. Tat is a regulatory protein that drastically enhances the efficiency of viral transcription. Tat stands for "Trans-Activator of Transcription". The protein consists of between 86 and 101 amino acids depending on the subtype. Tat vastly increases the level of transcription of the HIV dsDNA. Before Tat is present, a small number of RNA transcripts will be made, which allow the Tat protein to be produced. Tat then binds to cellular factors and mediates their phosphorylation, resulting in increased transcription of all HIV genes, providing a positive feedback cycle. This in turn allows HIV to have an explosive response once a threshold amount of Tat is produced, a useful tool for defeating the body's response.

Vectors in gene therapy

Gene therapy utilizes the delivery of DNA into cells, which can be accomplished by several methods, summarized below. The two major classes of methods are those that use recombinant viruses and those that use naked DNA or DNA complexes.

Synthetic biopolymers are human-made copies of biopolymers obtained by abiotic chemical routes. Synthetic biopolymer of different chemical nature have been obtained, including polysaccharides, glycoproteins, peptides and proteins, polyhydroxoalkanoates, polyisoprenes.

References

  1. Howard E. Davis; Jeffery R. Morgan; Martin L. Yarmush (2002). "Polybrene increases retrovirus gene transfer efficiency by enhancing receptor-independent virus adsorption on the target cell membranes". Biophysical Chemistry. 97 (2): 159–172. doi:10.1016/S0301-4622(02)00057-1. PMID   12050007.
  2. Howard E. Davis; Matthew Rosinski; Jeffrey R. Morgan; Martin L. Yarmush; et al. (2004). "Charged Polymers Modulate Retrovirus Transduction via Membrane Charge Neutralization and Virus Aggregation". Biophysical Journal. 86 (2): 1234–42. Bibcode:2004BpJ....86.1234D. doi:10.1016/S0006-3495(04)74197-1. PMC   1303915 . PMID   14747357.
  3. 1 2 "Polybrene Infection / Transfection Reagent | TR-1003-G". www.emdmillipore.com. Retrieved 2016-12-02.
  4. Hunkapiller, M. W.; Hood, L. E. (1978-05-30). "Direct microsequence analysis of polypeptides using an improved sequenator, a nonprotein carrier (polybrene), and high pressure liquid chromatography". Biochemistry. 17 (11): 2124–2133. doi:10.1021/bi00604a016. ISSN   0006-2960. PMID   667015.
  5. 1 2 Cooney, A.; Mann, T.J. (June 1999). "Recent experiences with hexadimethrine for neutralizing heparin after cardiopulmonary bypass". Anaesthesia and Intensive Care. 27 (3): 298–300. doi: 10.1177/0310057X9902700314 . PMID   10389567.
  6. Randsell, HT; Haller, JA; Stowens, DD; Barton, PB (1965). "Renal toxicity of polybrene (hexadimethrine bromide)". J Surg Res. 5 (5): 195–199. doi:10.1016/S0022-4804(65)80086-5. PMID   14281435.