673-06-3 Usage
Description
D-Phenylalanine, also known as D-alpha-Amino-beta-phenylpropionic acid, is a non-proteinogenic amino acid that functions as an inhibitor of enzymes that inactivate enkephalins, which are naturally occurring morphine-like peptides that help reduce pain. By blocking the degradation of enkephalins, D-Phenylalanine can effectively reduce pain severity. It is one of the two isomers of phenylalanine, the other being L-Phenylalanine, and both have unique benefits. DL-Phenylalanine is a combination of both "L" and "D" forms, offering the advantages of both types.
Uses
Used in Pharmaceutical Industry:
D-Phenylalanine is used as an analgesic agent for its ability to reduce pain severity by inhibiting enkephalin degradation, making it a potential candidate for pain management and relief of chronic pain conditions such as rheumatoid arthritis.
Used in Neurotransmitter Synthesis:
D-Phenylalanine is used as a precursor in the synthesis of neurotransmitters, which play a crucial role in the communication between nerve cells and can have an impact on mood and cognitive function.
Used in Antitubercular Drug Design:
D-Phenylalanine is used in the synthesis of Schaeffer's acid analogues, which are important structures in the development of tuberculostatic drugs. These analogues exhibit the ability to inhibit Mycobacterium tuberculosis type II dehydroquinase, contributing to the fight against tuberculosis.
Used in Nutritional Supplements:
DL-Phenylalanine, which contains both Land D-Phenylalanine, is used as a dietary supplement to provide the benefits of both isomers, including pain relief and neurotransmitter synthesis.
In vitro
The binding of D-Phenylalanine to carboxypeptidase A confers anion sensitivity upon the function of the enzyme by breaking the hydrogen bond between the active site base, Glu-270, and the zinc-bound water molecule.
In vivo
D-Phenylalanine (500 mg/kg p.o.) produces a small increase in aversive threshold which is not statistically significant and not naloxone reversible. Acetylsalicylic acid (200 mg/kg p.o.) but not zomepirac sodium (200 mg/kg p.o.) in combination with D-phenylalanine (500 mg/kg) produces a small statistically significant increase in aversive threshold.
Biological Activity
DL-Phenylalanine (DLPA) is marketed as a nutritional supplement for its purported analgesic and antidepressant activities. DL-Phenylalanine is a mixture of D-phenylalanine and L-phenylalanine. The reputed analgesic activity of DL-phenylalanine may be explained by the possible blockage by D-phenylalanine of enkephalin degradation by the enzyme carboxypeptidase A. The mechanism of DL-phenylalanine's supposed antidepressant activity may be accounted for by the precursor role of L-phenylalanine in the synthesis of the neurotransmitters norepinephrine and dopamine. Elevated brain levels of norepinephrine and dopamine are thought to have an antidepressant effect. D-Phenylalanine is absorbed from the small intestine and transported to the liver via the portal circulation. A small amount of D-phenylalanine appears to be converted to L-phenylalanine. D-Phenylalanine is distributed to the various tissues of the body via the systemic circulation. It appears to cross the blood–brain barrier less efficiently than L-phenylalanine, and so a small amount of an ingested dose of D-phenylalanine is excreted in the urine without penetrating the central nervous system.
Benefits
D-phenylalanine (DPA) decreases pain by blocking the enzymes that break down the body's natural painkillers. Clinical studies suggest DPA may inhibit some types of chronic pain.Certain amino acids have been found to raise pain thresholds and increase tolerance to pain. One of these, a synthetic amino acid called D-phenylalanine (DPA), decreases pain by blocking the enzymes that break down endorphins and enkephalins, the body's natural pain-killing chemicals. DPA may also produce pain relief by other mechanisms, which are not well understood.In animal studies, DPA decreased chronic pain within 15 minutes of administration and the effects lasted up to six days. It also decreased responses to acute pain. These findings have been independently verified in at least five other studies. Clinical studies on humans suggest DPA may inhibit some types of chronic pain, but it has little effect on most types of acute pain.
Side Effects
Phenylalanine is found in many protein-containing foods and is “generally recognized as safe” by the Food and Drug Administration (FDA).
The amount of this amino acid found in foods should not pose a risk for otherwise healthy individuals.
What’s more, few or no side effects are generally observed at supplement doses of 23–45 mg per pound (50–100 mg per kg) of body weight.
However, it may be best for pregnant women to avoid taking phenylalanine supplements.
Reactivity Profile
D-alpha-Amino-beta-phenylpropionic acid may be light sensitive. D-alpha-Amino-beta-phenylpropionic acid reacts with strong oxidizing agents, acids and bases. . Act as weak acids in solution.
Fire Hazard
Flash point data for D-alpha-Amino-beta-phenylpropionic acid are not available, however D-alpha-Amino-beta-phenylpropionic acid is probably combustible.
Pharmacokinetics
D-Phenylalanine is the synthetic dextro isomer of phenylalanine, an essential amino acid with anti-depressant and analgesic activities. D-Phenylalanine is converted into tyrosine and tyrosine in turn is converted into L-dopa, norepinephrine, and epinephrine, three key neurotransmitters. As a result this agent is associated with elevated levels of the neurotransmitters dopamine and norepinephrine in the brain, which may alleviate symptoms of depression. In addition, as an inhibitor of enkephalinase, which metabolizes endorphins, D-phenylalanine may be used to treat chronic pain through blocking the break down of endorphins (natural pain killers).
Safety Profile
Mildly toxic by intraperitoneal route. Human systemic effects by ingestion: nausea, hypermotility, diarrhea. When heated to decomposition it emits toxic fumes of NOx.
References
https://www.alfa.com/en/catalog/A10572/
https://en.wikipedia.org/wiki/Phenylalanine
Christianson, D. W., et al. "Binding of D-phenylalanine and D-tyrosine to carboxypeptidase A. " Journal of Biological Chemistry264.22(1989):12849-53.
Check Digit Verification of cas no
The CAS Registry Mumber 673-06-3 includes 6 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 3 digits, 6,7 and 3 respectively; the second part has 2 digits, 0 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 673-06:
(5*6)+(4*7)+(3*3)+(2*0)+(1*6)=73
73 % 10 = 3
So 673-06-3 is a valid CAS Registry Number.
InChI:InChI=1/C9H11NO2/c10-8(9(11)12)6-7-4-2-1-3-5-7/h1-5,8H,6,10H2,(H,11,12)/t8-/m1/s1
673-06-3Relevant articles and documents
Protein Engineering of d-Succinylase from Cupriavidus sp. for d-Amino Acid Synthesis and the Structural Implications
Azuma, Masayuki,Kumagai, Shinya,Nishiya, Yoshiaki,Sumida, Yosuke,Yamada, Toshihide,Yamasaki, Masayuki
, p. 4770 - 4778 (2021/08/30)
d-Amino acids are important chiral building blocks for pharmaceuticals and agrochemicals. Previously, we have used d-Succinylase (DSA) from Cupriavidus sp. P4-10-C and N-succinyl amino acid racemase (NSAR, EC.4.2.1.113) from Geobacillus stearothermophilus NCA1503 to produce d-amino acids via the dynamic kinetic resolution of N-succinyl-dl-amino acids. However, the use of this bioconversion system remains challenging for industrial application due to the insufficient enantioselectivity of DSA toward N-succinyl-d-amino acids. Therefore, we screened DSA mutants for improved enantioselectivity by directed evolution. Several mutants showed improved enantioseletivity compared to wild-type DSA. L182E mutant had superior enantioselectivity, and the thermal stability was also remarkably improved by this single mutation. We solved the crystal structure of the L182E mutant in complex with succinic acids at a resolution 2.0 ?. The mutated residues in all generated mutants that showed improved enantioselectivity (including the substituted Glu182 in the L182E mutant) are found very close to the active site. The solved crystal structure also provides some rationale to explain the higher thermostability of the L182E mutant compared to wild-type DSA. d-phenylalanine and d-tryptophan were produced in high conversion (approximately 90%) with 98.8% ee and 99.6% ee, respectively, using coupled L182E DSA and NSAR with the one-pot enzymatic method. These data suggested that L182E DSA may be a useful biocatalyst for industrial d-amino acids production. (Figure presented.).
Highly Stable Zr(IV)-Based Metal-Organic Frameworks for Chiral Separation in Reversed-Phase Liquid Chromatography
Jiang, Hong,Yang, Kuiwei,Zhao, Xiangxiang,Zhang, Wenqiang,Liu, Yan,Jiang, Jianwen,Cui, Yong
supporting information, p. 390 - 398 (2021/01/13)
Separation of racemic mixtures is of great importance and interest in chemistry and pharmacology. Porous materials including metal-organic frameworks (MOFs) have been widely explored as chiral stationary phases (CSPs) in chiral resolution. However, it remains a challenge to develop new CSPs for reversed-phase high-performance liquid chromatography (RP-HPLC), which is the most popular chromatographic mode and accounts for over 90% of all separations. Here we demonstrated for the first time that highly stable Zr-based MOFs can be efficient CSPs for RP-HPLC. By elaborately designing and synthesizing three tetracarboxylate ligands of enantiopure 1,1′-biphenyl-20-crown-6, we prepared three chiral porous Zr(IV)-MOFs with the framework formula [Zr6O4(OH)8(H2O)4(L)2]. They share the same flu topological structure but channels of different sizes and display excellent tolerance to water, acid, and base. Chiral crown ether moieties are periodically aligned within the framework channels, allowing for stereoselective recognition of guest molecules via supramolecular interactions. Under acidic aqueous eluent conditions, the Zr-MOF-packed HPLC columns provide high resolution, selectivity, and durability for the separation of a variety of model racemates, including unprotected and protected amino acids and N-containing drugs, which are comparable to or even superior to several commercial chiral columns for HPLC separation. DFT calculations suggest that the Zr-MOF provides a confined microenvironment for chiral crown ethers that dictates the separation selectivity.
Reconstruction of Hyper-Thermostable Ancestral L-Amino Acid Oxidase to Perform Deracemization to D-Amino Acids
Ishida, Chiharu,Miyata, Ryo,Hasebe, Fumihito,Miyata, Azusa,Kumazawa, Shigenori,Ito, Sohei,Nakano, Shogo
, p. 5228 - 5235 (2021/11/05)
L-amino acid oxidases (LAAOs) with broad substrate specificity can be used in the deracemization of D,L-amino acids (D,L-AAs) to their D-enantiomers. Hyper-thermostable LAAO (HTAncLAAO) was designed through a combination of manual sequence data mining and ancestral sequence reconstruction. Soluble expression of HTAncLAAO (>50 mg/L) can be achieved using an E. coli system. HTAncLAAO, which recognizes seven L-AAs as substrates, exhibits extremely high thermal stability and long-term stability; the t1/2 value was 95 °C and 99 % ee, D-enantiomer). These results suggest that HTAncLAAO is an excellent biocatalyst to perform this deracemization.