Propargylglycine

Propargylglycine
L-Propargylglycine
Names
IUPAC name
(2S)-2-Aminopent-4-ynoic acid
Other names
2-Propynylglycine
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.245.847
EC Number
  • L: 812-854-9
KEGG
UNII
  • L: InChI=1S/C5H7NO2/c1-2-3-4(6)5(7)8/h1,4H,3,6H2,(H,7,8)/t4-/m0/s1
    Key: DGYHPLMPMRKMPD-BYPYZUCNSA-N
  • DL: InChI=1S/C5H7NO2/c1-2-3-4(6)5(7)8/h1,4H,3,6H2,(H,7,8)
    Key: DGYHPLMPMRKMPD-UHFFFAOYSA-N
  • L: C#CC[C@@H](C(=O)O)N
  • DL: C#CCC(C(=O)O)N
Properties
C5H7NO2
Molar mass 113.116 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

Propargylglycine is a non-proteinogenic amino acid found in a variety of organisms including Amanita mushrooms[1] and the bacteria Streptomyces cattleya.[2] It is a toxin that interferes with the metabolism of sulfur-containing amino acids via inhibition of cystathionine γ-lyase (also known as cystathionase or CSE).[3][4]

Structure and properties

Propargylglycine is a is non-proteinogenic amino acid that features an unusual terminal alkyne group. It is chemically related to β-ethynylserine, with which it shares a biosynthetic pathway,[5] and to cyanoalanine. Propargylglycine is useful in click chemistry applications.[6][7]

Biological activity

Propargylglycine acts as an irreversible inhibitor of cystathionine γ-lyase (CSE), an enzyme that catalyzes the breakdown of cystathionine to cysteine and is involved in the endogenous production of hydrogen sulfide (H2S). It functions as a mechanism-based inactivator, forming a covalent adduct with the enzyme's pyridoxal 5'-phosphate (PLP) cofactor. Due to its inhibition of CSE, propargylglycine is widely used as a research tool to study the biological roles of H2S in processes such as vasodilation, inflammation, oxidative stress, and various disease models (e.g., hypertension, renal injury, myocardial protection, and hypoxic responses).[8][9][10]

It also inhibits other PLP-dependent enzymes such as methionine γ-lyase (MGL) and alanine transaminase (ALT).[11]

References

  1. ^ Kawaji, Akiko; Yamauchi, Kiyotaka; Fujii, Shinobu; Natsuki, Reiko; Takabatake, Eigo; Yamaura, Yoshio (1992). "Effects of Mushroom Toxins on Glycogenolysis; Comparison of Toxicity of Phalloidin, .ALPHA.-Amanitin and DL-Propargylglycine in Isolated Rat Hepatocytes". Journal of Pharmacobio-Dynamics. 15 (3): 107–112. doi:10.1248/bpb1978.15.107. PMID 1320679.
  2. ^ Kuehnel, Karin (2019). "A bacterial treasure trove". Nature Methods. 16 (5): 360. doi:10.1038/s41592-019-0411-1. PMID 31040424.
  3. ^ Piotrowska, M.; Paszewski, A. (1986). "Propargylglycine as a Fungal Inhibitor: Effect on Sulphur Amino Acid Metabolism". Microbiology. 132 (10): 2753–2760. doi:10.1099/00221287-132-10-2753.
  4. ^ Abeles, Robert H.; Walsh, Christopher T. (1973). "Acetylenic enzyme inactivators. Inactivation of .gamma.-cystathionase, in vitro and in vivo by propargylglycine". Journal of the American Chemical Society. 95 (18): 6124–6125. Bibcode:1973JAChS..95.6124A. doi:10.1021/ja00799a053. PMID 4733835.
  5. ^ Marchand, J. A.; Neugebauer, M. E.; Ing, M. C.; Lin, C.-I.; Pelton, J. G.; Chang, M. C. Y. (2019). "Discovery of a pathway for terminal-alkyne amino acid biosynthesis". Nature. 567 (7748): 420–424. Bibcode:2019Natur.567..420M. doi:10.1038/s41586-019-1020-y. PMID 30867596.
  6. ^ Lutz, Jean-François; Börner, Hans G.; Weichenhan, Katja (2006). "Combining ATRP and "Click" Chemistry: A Promising Platform toward Functional Biocompatible Polymers and Polymer Bioconjugates". Macromolecules. 39 (19): 6376–6383. Bibcode:2006MaMol..39.6376L. doi:10.1021/ma061557n.
  7. ^ Otsuka, Hono; Fujishiro, Takashi (2025). "Mechanism and Utility of the ATP-Grasp Enzyme BesA for the Synthesis of Non-natural Alkyne-Containing Dipeptides Applicable for Click Chemistry". ACS Chemical Biology. 20 (10): 2521–2532. doi:10.1021/acschembio.5c00676. PMID 41047544.
  8. ^ Ohta, J.; Ubuka, T.; Kodama, H.; Sugahara, K.; Nagamine, N. (1997). "A new metabolite of propargylglycine, gamma-glutamylpropargylglycylglycine, in liver of D,L-propargylglycine-administered rats". Biochimica et Biophysica Acta (BBA) - General Subjects. 1334 (2–3): 240–246. doi:10.1016/s0304-4165(96)00100-6. PMID 9101719.
  9. ^ Zhou, X.; Tang, S.; Hu, K.; Zhang, Z.; Liu, P.; Luo, Y.; Kang, J.; Xu, L. (2018). "DL-Propargylglycine protects against myocardial injury induced by chronic intermittent hypoxia through inhibition of endoplasmic reticulum stress". Sleep & Breathing = Schlaf & Atmung. 22 (3): 853–863. doi:10.1007/s11325-018-1656-0. PMID 29770919.
  10. ^ Oosterhuis, N. R.; Frenay, A. R.; Wesseling, S.; Snijder, P. M.; Slaats, G. G.; Yazdani, S.; Fernandez, B. O.; Feelisch, M.; Giles, R. H.; Verhaar, M. C.; Joles, J. A.; Van Goor, H. (2015). "DL-propargylglycine reduces blood pressure and renal injury but increases kidney weight in angiotensin-II infused rats". Nitric Oxide : Biology and Chemistry. 49: 56–66. doi:10.1016/j.niox.2015.07.001. PMID 26192363.
  11. ^ Echizen, Honami; Hanaoka, Kenjiro; Shimamoto, Kazuhito; Hibi, Ryota; Toma-Fukai, Sachiko; Ohno, Hisashi; Sasaki, Eita; Komatsu, Toru; Ueno, Tasuku; Tsuchiya, Yukihiro; Watanabe, Yasuo; Otsuka, Takao; Saito, Hiroaki; Nagatoishi, Satoru; Tsumoto, Kouhei; Kojima, Hirotatsu; Okabe, Takayoshi; Shimizu, Toshiyuki; Urano, Yasuteru (2023). "Discovery of a cystathionine γ-lyase (CSE) selective inhibitor targeting active-site pyridoxal 5′-phosphate (PLP) via Schiff base formation". Scientific Reports. 13 (1) 16456. doi:10.1038/s41598-023-43536-6. PMC 10542788. PMID 37777556.
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