Name: (4S)-4-Azido-D-proline
Brand: BOC Sciences
Rating: 5 (1 reviews)

Synonyms

(S)-4-Azido-D-proline; H-Pro(4-N3) (2R,4S); H-D-Pro(4-N3) (2R,4S); H-D-Pro(4-N3)-OH (2R,4S); H-Pro(4-N3)-OH (2R,4S); (2R,4S)-H-D-Pro(4-N3)-OH

IUPAC Name

(2R,4S)-4-azidopyrrolidine-2-carboxylic acid

Canonical SMILES

C1[C@@H](CN[C@H]1C(=O)O)N=[N+]=[N-]

InChI

InChI=1S/C5H8N4O2/c6-9-8-3-1-4(5(10)11)7-2-3/h3-4,7H,1-2H2,(H,10,11)/t3-,4+/m0/s1

InChIKey

PPRFZPZRQYPCER-IUYQGCFVSA-N

Melting Point

148-151°C

Appearance

White crystalline powder

Storage

Store at 2-8 °C

(4S)-4-Azido-D-Proline hydrochloride, a specialized chemical compound, boasts a myriad of applications in bioscience research and the medical field. Here are four key applications presented with a high degree of perplexity and burstiness:

Protein Engineering: Utilizing (4S)-4-Azido-D-Proline hydrochloride as a foundational element in protein engineering allows for the introduction of azido groups into peptides and proteins. This bioorthogonal handle enables subsequent chemical modifications like click chemistry, facilitating labeling, tracking, and functional studies of proteins across diverse biological systems. The versatility of this compound in protein engineering opens up new avenues for investigating complex biological processes with intricate molecular interactions.

Drug Development: In the realm of pharmaceutical innovation, (4S)-4-Azido-D-Proline hydrochloride plays a pivotal role in developing novel drugs. Its incorporation into drug molecules enhances binding affinity and stability, ultimately improving drug efficacy and pharmacokinetic properties. The introduction of the azido group simplifies the attachment of additional functional groups, offering possibilities for enhancing drug formulations and targeting specific biological pathways. This compound stands at the forefront of drug discovery, driving advancements in therapeutic interventions with promising outcomes.

Bioconjugation: Widely applied in bioconjugation techniques, (4S)-4-Azido-D-Proline hydrochloride facilitates the linking of biomolecules, such as proteins and nucleic acids, to various surfaces and labels. The azido group's efficient reactivity with alkyne-functionalized molecules via click chemistry results in stable triazole linkages, critical for developing cutting-edge diagnostic tools, biosensors, and targeted drug delivery systems. This application underscores the compound's significance in enabling precise molecular connections and advancing bioanalytical methodologies in bioscience research.

Chemical Biology: Within the realm of chemical biology, (4S)-4-Azido-D-Proline hydrochloride emerges as a valuable tool for studying intricate biological processes. Integrating this compound into biological macromolecules enables researchers to probe interactions and dynamics within cellular systems. The unique site provided by the azido group enables selective modifications, facilitating in-depth investigations into protein functions and cellular pathways. This application sheds light on the compound's pivotal role in unraveling the complexities of cellular mechanisms, offering insights into fundamental biological processes with nuanced precision.

1. Discovery of (1S,2R,3S,4S,5R,6R)-2-Amino-3-[(3,4-difluorophenyl)sulfanylmethyl]-4-hydroxy-bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid Hydrochloride (LY3020371·HCl): A Potent, Metabotropic Glutamate 2/3 Receptor Antagonist with Antidepressant-Like Activity

Mark D Chappell, et al. J Med Chem. 2016 Dec 22;59(24):10974-10993. doi: 10.1021/acs.jmedchem.6b01119. Epub 2016 Dec 6.

As part of our ongoing efforts to identify novel ligands for the metabotropic glutamate 2 and 3 (mGlu2/3) receptors, we have incorporated substitution at the C3 and C4 positions of the (1S,2R,5R,6R)-2-amino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid scaffold to generate mGlu2/3 antagonists. Exploration of this structure-activity relationship (SAR) led to the identification of (1S,2R,3S,4S,5R,6R)-2-amino-3-[(3,4-difluorophenyl)sulfanylmethyl]-4-hydroxy-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid hydrochloride (LY3020371·HCl, 19f), a potent, selective, and maximally efficacious mGlu2/3 antagonist. Further characterization of compound 19f binding to the human metabotropic 2 glutamate (hmGlu2) site was established by cocrystallization of this molecule with the amino terminal domain (ATD) of the hmGlu2 receptor protein. The resulting cocrystal structure revealed the specific ligand-protein interactions, which likely explain the high affinity of 19f for this site and support its functional mGlu2 antagonist pharmacology. Further characterization of 19f in vivo demonstrated an antidepressant-like signature in the mouse forced-swim test (mFST) assay when brain levels of this compound exceeded the cellular mGlu2 IC50 value.

2. Serotonin-1A receptor dependent modulation of pain and reward for improving therapy of chronic pain

Darakhshan Jabeen Haleem Pharmacol Res. 2018 Aug;134:212-219. doi: 10.1016/j.phrs.2018.06.030. Epub 2018 Jun 30.

Chronic pain conditions such as low back pain and osteoarthritis are the most prominent causes of disability worldwide. Morphine and other opioid drugs are the gold standard treatment for severe pain, including surgical pain, but the use of these drugs for chronic pain is limited largely because long term use of these drugs is associated with drug abuse and hyperalgesia which produces a negative impact on the treatment. Non-addictive treatments for chronic pain are, therefore, highly needed. Commonly used opioid drugs activate mu opioid receptors, resulting in an inhibition of tonic activity of nociceptive neurons. The rewarding effects of opioid drugs are also mediated via activation of mu opioid receptors and inhibition of GABA mediated control of the activity of dopamineregic neurons. Enhanced glutamate release and greater activity of NMDA glutamate receptors is linked to the hyperalgesic effects of opioid drugs. Evidence suggests that activation of serotonin (5-hydroxytryptamine; 5-HT)-1 A receptors modulates dopamine neurotransmission to inhibit rewarding effects of drugs of abuse. Activation of these receptors inhibits glutamate release from the sensory neurons to reduce pain transmission. To help develop strategies for improving therapeutics in chronic pain, and draw research interest in the synthesis of non-addictive opioid drugs which do not predispose to hyperalgesia, the present article concerns the potential mechanism involved in 5-HT-1 A receptor mediated inhibition of pain and reward.

3. Combinatorial solution-phase synthesis of (2S,4S)-4-acylamino-5-oxopyrrolidine-2-carboxamides

Crt Malavasic, Blaz Brulc, Petra Cebasek, Georg Dahmann, Niklas Heine, David Bevk, Uros Groselj, Anton Meden, Branko Stanovnik, Jurij Svete J Comb Chem. 2007 Mar-Apr;9(2):219-29. doi: 10.1021/cc060114s.

Solution-phase combinatorial synthesis of (2S,4S)-4-acylamino-5-oxopyrrolidine-2-carboxamides was studied. First, di-tert-butyl (2S,4S)-4-amino-5-oxopyrrolidine-1,2-dicarboxylate hydrochloride was prepared as the key intermediate in five steps from (S)-pyroglutamic acid. Acylation of the amino group followed by acidolytic deprotection gave (2S,4S)-4-acylamino-5-oxopyrrolidine-2-carboxylic acids, which were then coupled with amines to furnish a library of (2S,4S)-4-acylamino-5-oxopyrrolidine-2-carboxamides. Four coupling reagents, BPC, EEDQ, TBTU, and PFTU, were tested for the amidation reactions in the final step. Amidations with EEDQ and TBTU led to the desired carboxamides. On the other hand, BPC and PFTU were not suited, since diketopiperazines were sometimes obtained instead of the desired carboxamides.