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Testosterone

Introduction


Testosterone (CAS 58-22-0) is a hormone that regulates a number of processes in the human body. In males, testosterone is secreted by the testes while in women it is secreted by the adrenal glands and ovaries, with some being made up through the peripheral conversion of another hormone, androstenedione.

Most testosterone is not freely available in the bloodstream, but is rather bound to either albumin or to sex hormone binding globulin (SHBG). Unbound testosterone and that bound to albumin are said to be active and bio-available, while testosterone bound to SHBG is unavailable and unable to perform its function.

The Function of Testosterone


Testosterone has a large number of functions both in males and in females, and a change in testosterone levels in the body can have profound effects. A low testosterone count can have the following effects:

      Delayed puberty in adolescents

      Hypogonadism in boys

      Testicular failure in adult males

      Erectile dysfunction in men

      Infertility in both men and women

Having an accurate count of testosterone levels for patients with these symptoms can be key in forming the correct diagnosis.

Testing for Testosterone


There are three testosterone measurements that are usually taken: the total testosterone, the free testosterone levels and the amount of bio-available testosterone.

Total testosterone levels are measures by mass spectrometry. This technique has the benefit of being rapid (analysis of a sample can take as little as four minutes) and has a very high sensitivity and specificity, with no cross-reactivity to other steroid compounds. The reportable range is very large, and encompasses the limits of human testosterone levels.

Free testosterone levels are measured through equilibrium dialysis which gives the percentage of free testosterone. The technique can be used to investigate the amount of protein bound to specific ligand, and then calculate the percentage of unbound ligand from that. The amount of free testosterone is then calculated from the total testosterone level found through LC/MS/MS.

Finally, the amount of bio-available testosterone can also be calculated from the constants for the binding of testosterone to SHBG through an immunochemiluminometric assay or the binding to albumin through spectrophotometry.

Complete testosterone data sets can help doctors form a diagnosis in the event of the symptoms described above. However, a number of factors can increase or decrease testosterone levels, such as drug use, and these should be considered as well.

In order to complete these tests analysis labs rely heavily on mass spectrometry for accurate analysis at trace content. As such IsoSciences synthesizes and has available both labeled and unlabeled forms of testosterone.

6066UNL unlabeled testosterone (unlabeled)

6066 13C-labeled Testosterone (13C3)

3009 D-labeled testosterone (D5)

These testosterone solutions are available as CertiMass solutions in order to increase efficiency of testing if that is required.

We are proud to offer a selection of stable labeled hormones. For your convenience, we sell unlabeled hormones alongside our list of labeled hormones. Our selection includes CertiMass™ Reference Standards, which are standard solutions for many of our premier compounds

If you are unable to find the desired hormone in our catalog, please contact us by email or phone (610-337-3762) we will be more than happy to provide a quote on custom synthetic work.

Testosterone

 

Isotope Labeling

There are many reasons to use custom-made isotope labeled organic molecules of all types. Isotopic labeling of compounds is a non-radioactive method of labeling, provides site-specific investigation of structures, makes molecules easily detectable by mass spectrometry and NMR, maintaining the physico-chemical properties of the target molecule, and is cost-effective and easy to use. Most commonly used isotopes are 2H (D), 13C, and 15N.

Biosynthetic isotopic labeling of compounds is an alternative to pure synthetic methodologies for isotope labeling. By uniformly labeling all carbon and nitrogen atoms with D, 13C and 15N, a single protein sample can provide a plethora of structural information such as dihedral distances and angles. Labeled compounds such as 13C-labeled glucose or glycerol and 15N-labeled ammonium chloride or ammonium chlorate can be readily incorporated into the growth media for protein expression. However, through selective labeling, carbon precursors containing only 13C-labeled sites can be incorporated into protein expression media. In the process, these sites are then converted, through enzymatic pathways, to predictable positions in amino acids, ending in selective and specific labeling of proteins.

In its gas form, deuterium can be introduced into organic molecules by catalytic reduction. When site-specific labeling is not necessary, deuterium can be catalytically added to carbon-carbon double or triple bonds, such as in the synthesis of chiral acetic acid (TDH*CCO2H). Through reduction, 2H can also be introduced with isotopic hydride by transition metal-mediated exchange. For methyl groups Alanine, Leu, and Val, site-specific 2H labeling is most commonly used and serves as an excellent way to investigate the dynamics of proteins and DNA.

Isotope labeled chemistries currently synthesized by IsoSciences catalog can be found here.If you are unable to find the desired labeled molecule in our catalog, please contact us by email or phone (610-337-3762) we will be more than happy to provide a quote on custom synthetic work.

Isotope Labeling | Custom Isotope Labeling

 

Tritiation Methods

The use of tritium (3H) as a radio-label for tracking metabolites is a powerful tool in analytic chemistry. In fact, it is the isotope of choice for thousands of different reactions. Depending on the precursor, tritiation can be accomplished in several ways. Tritium is incorporated as radiolabel into organic molecules through a number of methods.

Exchange Reactions


In the simplest process, the labeling of such compounds as nucleotides, pyrimidines and alkaloids is easily, if somewhat inefficiently, accomplished by exposure to the appropriate amount of tritiated water. Any labile tritium is then removed and the product assayed for total activity.

For carbohydrates, nucleosides, amino acids and compounds containing benzylic protons, it is necessary to use a hydrogen transfer catalyst to obtain a satisfactory level of total activity in the tritiation. Similar to the above process, the labile tritium gas must also be evacuated at the end of the procedure but usually results in far higher total activity.

Known more familiarly as the Wilzbach method, this procedure simply involves the exposure of the substrate to isotopically pure tritium in a sealed, non-reactive container for several weeks. Since the reaction is promoted by the radioactive decay of the tritium, it is extremely destructive to the precursors and is rarely used.

Direct Synthesis


Molecule synthesis can be completed using tritium gas as a reducing or dehalogenating agent or reduction with borohydride.

Recent developments using activated spillover tritium in conjunction with a high-temperature, solid-state catalytic isotopic exchange procedure have shown remarkable – read, very pure – results with aliphatic compounds, steroids, and peptides.

The replacement of a halide, most usually of bromine and chlorine,with tritium in this process is preferred for use on heterocyclic aromatic especially purines and pyrimidines. It is quite efficient and easily achieves total activities equal or greater than standard solvent technique. Borohydride reduction is particularly well-suited for the labeling of carbohydrates and usually uses tritiated sodium borohydride, although it often results in relatively low levels of total activity.

Our experienced analytical group is able to use these methods coupled with orthogonal analytical methodologies and specific activity determinations in order to provide accurate and conclusive evidence to supportive final product delivery.

Our team is ready to discuss your needs and reliably deliver your compound with time and cost efficiency. Please contact the radiolabeling group at 610-337-3762 or Email .

Tritiation Methods | How Tritiation is Done

 

Labeled Gontyautoxin

Gonyautoxin is a phytotoxin with paralyzing effects produced by several flagellate protists, called dinoflagellates. Included in the group of saxitoxin-related chemical compounds,Gonyautoxin is specifically produced by Gonyaulax catenella, Gonyaulax tamarensis, and some other Protogonyaulax species. Usually, this compound is isolated from shellfish and, along with Saxitoxin, is the neurotoxin responsible for shellfish poisoning.

This potentially dangerous organic compound can be chemically classified into the aliphatic heteropolycyclic compounds super-class and further into the Saxitoxins,Gonyautoxins, and derivatives class. Considered a toxic substance as-is, Gonyautoxin is usually found in the cytoplasm and the extracellular fluid. Its predicted physico-chemical properties include a water solubility value of 3.05 g/L and a polar surface area. Other properties, such as the melting or boiling point have not been studied in depth yet.

Although at certain doses Gonyautoxin can be lethal, in extremely low doses it is considered to be highly beneficial in treating a few health conditions. Its high toxicity, and the cause of toxin-induced acute paralytic illness, is due to a reversible bind to receptor sites that are located on the voltage-gated sodium channel on excitable cells, phenomenon that causes a block in neuronal transmission. Thus, applying small amounts of paralyzing Gonyautoxin to restricted areas will lead to a temporary paralysis of the striated muscle in question, the effect being dependent on the dose.

Gonyautoxin has mainly been used for medical purposes, in treating acute and chronic anal fissures. The paralytic action of the toxin was used for relieving the major symptoms of anal fissures, such as permanent pain, intense pain that accompanies the defecation process, and sphincter cramps. For example, the patients who participated in a study were administered doses of 100 units of Gonyautoxin in volumes of 1 ml. These were infiltrated into the sides of the anal fissure. The study showed that total remission of both acute and chronic fissures was achieved within up to 28 days.

Gonyautoxin was also used for treating chronic tension-type headaches. Patients who experienced this type of headaches for more than 15 days a month were locally injected with 50 micrograms of Gonyautoxin. The patients who underwent this form of treatment reported a significant decrease in pain and frequency of headache episodes. Also, no side effects were reported during the follow-up period. It was concluded that over 70 percent of the patients treated with Gonyautoxin have responded very well to the treatment.

If your studies or interests require the use of these, or related, toxins please contact the IsoSciences staff. IsoSciences supplies CertiMass solutions of Saxitoxin for analytical and R&D purposes and we may already have the labeled toxin available in our synthetic database and catalog. We can discuss how the IsoSciences chemists can work with your team to custom synthesize a new material should it be required.

You are also welcome to review our online catalog of related molecules utilized for related research and assay standards. The catalog can also be downloaded for easy reference.

Labeled Gontyautoxin | Gontyautoxin Labeling

 

Hydroxycorticosterone

This is a compound that is primarily used for pharmacological use. 18-Hydroxycorticosterone (CAS 561-65-9) has chemical makeup of C21H30O5, it is also known as 20-dione, 11beta, 21-trihydroxy-4-pregnene-3 among other synonyms. IIt is derived from corticosterone. It is primarily used in the synthesis of aldosterone with aldosterone synthase.

Biological Uses


In the human body, hydroxycorticosterone is used by the aldosterone synthase enzyme found in zona glomerulosa. This enzyme is used in the process of creating aldosterone. This is a steroid hormone found in the adrenal cortex of the adrenal glands, used in the regulating blood pressure by increasing absorption rates of water and ions in the kidney, leading to the secretion of potassium, and consequent conservation of sodium, which ultimately regulates blood pressure in the body.


It is therefore naturally located in extracellular and membranes, blood, and the adrenal gland. Abnormal quantities in the blood lead to terminal aldosterone biosynthesis defects.

Medical use of Synthetic Hydroxycorticosterone


It is used in a differential diagnosis of hyperaldosteronism because of adrenal adenoma. This is tested in patients with preexisting hypertension, abnormal renal-potassium wastage, and hypokalemia. Both bilateral hyperplasia and adrenal adenoma are known to increase the levels of 18-Hydroxycorticosterone, but using serum levels of 18-OH B from predetermined levels, bilateral hyperplesia can be ruled out.

The detection of Hydroxycorticosterone levels is done through extraction, then subjected to chromatography and a radio-immunoassay. or mass spectrometry. To assist labs with the detection and accurate analysis of this hormone, IsoSciences synthesizes and supplies unlabeled and labeled forms of this molecule.


8066UNL         Unlabeled Hydroxycorticosterone (CAS 561-65-9)

8066                D-labeled Hydroxycorticosterone (CAS 1257742-38-3; d4)      


We are proud to offer a selection of stable labeled hormones. For your convenience, we sell unlabeled hormones alongside our list of labeled hormones. Our selection includes CertiMass™ Reference Standards, which are standard solutions for many of our premier compounds


If you are unable to find the desired hormone in our catalog, please contact us by email or phone (610-337-3762) we will be more than happy to provide a quote on custom synthetic work.

Hydroxycorticosterone

 

Labeled Saxitoxin

Saxitoxin (C10H17N7O4) is among the best known neurotoxins and the most potent known sodium channel blocking agent. Saxitoxin has been called the most deadly non-protein toxin, and cannot be removed from food through standard means. Commonly produced by marine dinoflagellates or freshwater cyanobacteria and bearing paralytic properties, saxitoxin is also sometimes referred to as abrin and used in bioterrorism.

Clarification of Terminology


Labeled SaxitoxinThe term "saxitoxin" can refer to a complete set of different but structurally similar neurotoxic substances, including but not limited to:

*Pure saxitoxin or STX

*neosaxitoxin or NSTX

*gonyautoxin or GTX

*decarbamoylsaxitoxin or dcSTX

Saxitoxin is extremely hazardous to mammalian life forms including humans, and military applications have been suggested due to saxitoxin's low dose lethality. Saxitoxin is the cause of Paralytic Shellfish Poisoning or PSP.

Underlying Pathology


Saxitoxin is a potentially lethal toxin in healthy adults, but has a higher mortality rate among children, the elderly and those with compromised immune systems. In cases where saxitoxin poisoning leads to death, the typical cause is generally respiratory failure.

The primary effect of Saxitoxin is the blockage of sodium pathways within its victims' neurons.  This causes a flaccid paralysis and tends to leave victims calm and conscious during the pathology's onset. The lethal dosage of saxitoxin is .57 mg if ingested orally.

Synthesis


Saxitoxin can be synthesized despite its many challenges. Since the 1970s methods have been successfully attempted. The earliest method of synthesizing a type of saxitoxin involved building a series of cyclic guanidines upon pyrrolidine. Another method involved a [3+2] cycloaddition to access the core and make a more scalable and efficient means of production.

One important aspect of saxitoxin production relies on a C-H amination and oxathiazinaneiminium ion equivalent originally developed in the Du Bois lab. Further aspects of production rely on a stereocontrolled condensation of a 9-member ring formation process and 19 steps from a base of commercially available (r)-glycerol acetamide. The importance of this method above prior ones is that this saxitoxin's result, while resulting in a smaller percentile yield, yielded non-racemic saxitoxin.

IsoSciences supplies CertiMass solutions of Saxitoxin for analytical and R&D purposes.

If your studies or interests require the use of these, or related, toxins please contact the IsoSciences staff. We may already have the labeled toxin available in our synthetic database and catalog, else we can discuss how the IsoSciences chemists we can work with your team to custom synthesize a new material.

You are also welcome to review our online catalog of related molecules utilized for related research and assay standards. The catalog can also be downloaded for easy reference.

Labeled Saxitoxin | Saxitoxin Labeling

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