Product Name: (6R)-5,6,7,8-Tetrahydro-L-biopterin dihydrochloride
CAS No.: 69056-38-8
Synonyms: BH4(hydrochloride);Sapropterin; Tetrahydrobiopterin; Tetrahydro-L-Biopterin (hydrochloride)
Chemical Name: 2-​amino-​6R-​(1R,​2S-​dihydroxypropyl)-​5,​6,​7,​8-​tetrahydro-​4(1H)-​pteridinone,​ dihydrochloride
Molecular Formula: C9H15N5O3.2(HCl)
Molecular Weight: 314.17
Appearance: Colorless to pale yellow powder
Assay: HPLC>98%

Natural cofactor for phenylalanine hydroxylase, tyrosine hydroxylase, tryptophan hydroxylase, and nitric oxide synthetase.

(6R)-5,6,7,8-Tetrahydrobiopterin dihydrochloride ((6R)-BH₄ ) is soluble in oxygen free water at 19.60 - 20.40 mg/ml and yields a clear to slightly hazy, colorless to faint yellow solution.

Application:

(6R)-BH₄ has been used as a buffer component for assaying tyrosine hydroxylase enzyme activity in mouse brain tissues. (6R)-BH₄ has also been identified as an activator compound from a LOPAC library screen using a fluorogenic α-glucosidase assay.

BH₄ is a required cofactor for all NOS isoforms. It binds to the enzyme at a ratio of 1:1 BH₄/subunit.

A cofactor of inducible nitric oxide synthase. Neuronal nitric oxide synthase has a highly specific site for tetrahydrobiopterin binding.

Synonyms: (6R)-BH4; BH4; 6R-BH4; Sapropterin dihydrochloride; Dapropterin;2-amino-6-(1,2-dihydroxypropyl)-5,6,7,8-tetrahydro-3H-pteridin-4-one;(6R)-2-amino-6-[(1R,2S)-1,2-dihydroxypropyl]-5,6,7,8-tetrahydro-4(3H)-Pteridinone hydrochloride; (6b)-5,6,7,8-Tetrahydro-L-biopterin dihydrochloride; BioMarin T 1401; Biopten; Kuvan; SUN 0588; Shiratori SN 0588
Chemical Name: 2-amino-6R-(1R,2S-dihydroxypropyl)-5,6,7,8-tetrahydro-4(1H)-pteridinone, dihydrochloride
CAS No.: 69056-38-8
Molecular Formula: C₉H₁₅N₅O₃^.2(HCl)
Molecular Weight: 314.17
Specifications: Purity: >99.5%

Description: White to Light yellow powder. Chemical reduction of biopterin yields two diastereoisomers, 6R- and 6S- BH4.6R-BH4 is the natural form of tetrahydrobiopterin.. The 6R,S- BH4 that we manufacture contains more than 70% of 6R- BH4 and 30% of 6S- BH4.

Biochemical functions: Tetrahydrobiopterin is a natural occurring cofactor of the aromatic amino acid hydroxylases and is involved in the synthesis of tyrosine and the neurotransmitters dopamine and serotonin. It is also essential for nitric oxide synthase catalysed oxidation of L-arginine to L-citrullin and nitric oxide. Tetrahydrobiopterin is involved in many other biochemical functions, many of which have been just recently discovered.

Solubility: 6R-and 6R,S-BH4.2HCl is freely soluble in water. The solubility of 6S-BH4.H2SO4 is 2.3g per 100g of water(220C). A 1mM solution of 6R-BH4. in water gives a PH of 3.0 and a 1 M solution of 6R-BH4.2 in water gives a PH of 0.45.

Analytical methods:

        HPLC conditions:  Column: Whatman Partisil 10SCX

                          Eluant: 30mM NaH2PO4 ,PH 3

                          Flow rate: 1.5ml/min

                          Wavelength: 254nm

                          Solution: 160mg BH4/100g H2O with degassed ascorbic acid solution(0.16%)

Analytical methods (contd.):

        UV:      ε267   16x103M-1cm-1 in 0.1N HCl

        TLC :    BH4 solutions are not stable in the presence of air to perform TLC.        

Stability: Tetrahydrobiopterin is very hygroscopic. It reacts with oxygen especially in neutral and alkaline solutions. Due to oxidation tetrahydrobiopterin solutions become yellow but at -200C or colder ,solutions are relatively stable. 0.1mM solutions of tetrahydrobiopterin in water are much less stable than 1mM solutions, i.e. after 1 hour open at room temperature , 0.1mM solutions degrade by about 25% whereas 1mM solutions degrade only by 2%. After 3 hours, 0.1mM solutions degrade by more than 60% and 1mM solutions degrade only by 10%. Dry powder has different stability depending on conditions, as described in the table below.
                                      RT                                   -20°C
 In ampoules          several months              several years
Storage: Storage conditions are not controlled during shipment and we cannot guarantee that the customer will receive the shipment within 6 weeks. There is no cause for concern when ampoules are delayed in the post as they are stable for several months at room temperature. Customers who have purchased BH4 in the past can estimate the time required for shipment.

On arrival we recommend that the powder is stored at -200C or colder. After an ampoule has been opened, the remainder should be put in a vial and then it can be stored in a freezer. Solutions of tetrahydrobiopterin should be prepared in oxygen free water with the lowest possible PH value and frozen as soon as possible. In order to increase the stability of BH4 solutions, ascorbic acid, DTT or other antioxidants, may be added.

Uses: Tetrahydrobiopterin, in tablet form, are used in the diagnosis and management of phenylketonuria(PKU). Tetrahydrobiopterin, in powder form is used in various laboratory studies. Because of its instability it is not suitable for the addition to nutritional supplements.                                   

Safety information: Tetrahydrobiopterin is known to be safe for the intended use. Avoid prolonged inhalation of the fine dust of tetrahydrobiopterin which is very acidic. Otherwise there are no special precautions required in handling this product.

Remarks: The information in this publication is based on our current knowledge and experience. It does not relieve users or processors from carrying out their own precautions and tests.