Name: Fmoc-azetidine-3-carboxylic acid
Brand: BOC Sciences
Rating: 5 (1 reviews)

Synonyms

Fmoc-3-azetidine carboxylic acid

IUPAC Name

1-(9H-fluoren-9-ylmethoxycarbonyl)azetidine-3-carboxylic acid

Canonical SMILES

C1C(CN1C(=O)OCC2C3=CC=CC=C3C4=CC=CC=C24)C(=O)O

InChI

InChI=1S/C19H17NO4/c21-18(22)12-9-20(10-12)19(23)24-11-17-15-7-3-1-5-13(15)14-6-2-4-8-16(14)17/h1-8,12,17H,9-11H2,(H,21,22)

InChIKey

QDEJCUHGSHSYQH-UHFFFAOYSA-N

Density

1.368 g/cm3

Melting Point

162-165 °C

Appearance

White or off-white powder

Quantity

Data not available, please inquire.

Storage

Store at 2-8 °C

Boiling Point

543.3°C at 760 mmHg

Fmoc-azetidine-3-carboxylic acid is a versatile compound known for its significant role in drug discovery, particularly as a cleavable Antibody-Drug Conjugate (ADC) linker and an alkyl chain-based PROTAC (PROteolysis TArgeting Chimeras) linker. The structural attributes of Fmoc-azetidine-3-carboxylic acid, which include the azetidine ring, impart unique properties that make it a valuable building block in pharmaceuticals. Its role in medicinal chemistry is of considerable interest due to the potential it offers in enhancing the delivery and specificity of therapeutic agents.

In the context of ADCs, Fmoc-azetidine-3-carboxylic acid serves as a key component in the design of linkers that connect a potent cytotoxic drug to an antibody. The efficacy of ADCs is highly dependent on the stability and cleavability of the linker in the biological environment. Fmoc-azetidine-3-carboxylic acid contributes to this by offering a balance between stability during circulation and efficient drug release within the target cells. The linkers based on this compound can be engineered to cleave in response to specific intracellular conditions such as the presence of certain enzymes or pH, thus enhancing the selectivity and reducing off-target effects.

Aside from ADC applications, Fmoc-azetidine-3-carboxylic acid is prominent in the development of PROTAC technologies. In PROTACs, the linker’s primary function is to connect the molecule that binds to the protein of interest with the ligand that recruits an E3 ubiquitin ligase, facilitating the degradation of the target protein. The alkyl chain aspect of the Fmoc-azetidine-3-carboxylic acid linker provides the necessary flexibility and spatial orientation needed to effectively bridge these two moieties. This strategic positioning is critical for the successful ubiquitination and subsequent proteasomal degradation of the target protein, offering a novel approach to modulating protein function.

The use of Fmoc-azetidine-3-carboxylic acid linkers in drug discovery is transformative because it enables the development of therapies that precisely target diseased cells while sparing normal ones, thereby improving therapeutic indices. The compound’s ability to contribute to the stability and functionality of drug candidates makes it a cornerstone in the design of modern biologics and small-molecule drugs. With the growing interest in personalized medicine, the specificity conferred by linkers such as those derived from Fmoc-azetidine-3-carboxylic acid is increasingly valuable, offering hope for more effective and safer treatments for complex diseases, including cancers and genetic disorders.

1.Serum Uric Acid Is Positively Associated with Handgrip Strength among Japanese Community-Dwelling Elderly Women.

Kawamoto R1,2, Ninomiya D1,2, Kasai Y2, Kusunoki T2, Ohtsuka N2, Kumagi T1, Abe M1. PLoS One. 2016 Apr 14;11(4):e0151044. doi: 10.1371/journal.pone.0151044.

Serum uric acid (UA) has strong anti-oxidant properties. Muscle strength and mass decrease with age, and recently, this decrease has been defined as sarcopenia. Sarcopenia may be triggered by oxidative stress. We investigated whether serum UA is associated with handgrip strength (HGS), which is a useful indicator of sarcopenia, among Japanese community-dwelling elderly persons. The present study included 602 men aged 72 ± 7 years and 847 women aged 71 ± 6 years from a rural village. We examined the cross-sectional relationship between serum UA and HGS. In both genders, HGS increased significantly with increased serum UA levels. A multiple linear regression analysis using HGS as an objective variable and various confounding factors as explanatory variables showed that in men age, drinking status, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and estimated glomerular filtration ratio (eGFRCKDEPI) were independently and significantly associated with HGS, and in women, serum UA as well as age, body mass index, drinking status, diastolic blood pressure, and eGFRCKDEPI were independently and significantly associated with HGS.

2.Neurochemical Changes Associated with Stress-Induced Sleep Disturbance in Rats: In Vivo and In Vitro Measurements.

Lee DW1,2, Chung S3, Yoo HJ4, Kim SJ4, Woo CW2, Kim ST2, Lee DH1, Kim KW5, Kim JK5, Lee JS5, Choi CG5, Shim WH5, Choi Y2, Woo DC2. PLoS One. 2016 Apr 14;11(4):e0153346. doi: 10.1371/journal.pone.0153346.

The goal of this study was to quantitatively assess the changes in the cerebral neurochemical profile and to identify those factors that contribute to the alteration of endogenous biomolecules when rats are subjected to stress-induced sleep disturbance. We exposed Sprague-Dawley rats (controls: n = 9; stress-induced sleep perturbation rats: n = 11) to a psychological stressor (cage exchange method) to achieve stress-induced sleep perturbation. In vivo magnetic resonance imaging assessments were carried out using a high-resolution 9.4 T system. For in vivo neurochemical analysis, a single voxel was localized in the right dorsal hippocampal region, and in vivo spectra were quantified for 17 cerebral neurochemical signals. Rats were sacrificed upon completion of the magnetic resonance spectroscopy protocol, and whole-brain tissue was harvested from twenty subjects. The dopamine and serotonin signals were obtained by performing in vitro liquid chromatography-tandem mass spectrometry on the harvested tissue.

3.Perfluoroalkylated substances effects in Xenopus laevis A6 kidney epithelial cells determined by ATR-FTIR spectroscopy and chemometric analysis.

Gorrochategui E, Lacorte S, Tauler R, Martin FL. Chem Res Toxicol. 2016 Apr 14. [Epub ahead of print]

The effects of four perfluoroalkylated substances (PFASs), namely, perfluorobutanesulfonate (PFBS), perfluorooctanoic acid (PFOA), perfluorooctanesulfonate (PFOS) and perfluorononanoic acid (PFNA) were assessed in Xenopus laevis A6 kidney epithelial cells by attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy and chemometric analysis. Principal component analysis-linear discriminant analysis (PCA-LDA) was used to visualize wavenumber-related alterations and ANOVA-simultaneous component analysis (ASCA) allowed data processing considering the underlying experimental design. Both analyses evidenced a higher impact of low-dose PFAS-treatments (10-9 M) on A6 cells forming monolayers, while there was a larger influence of high-dose PFAS-treatments (10-5 M) on A6 cells differentiated into dome structures. The observed dose-response PFAS-induced effects were to some extent related to their cytotoxicity: the EC50-values of most influent PFAS-treatments increased (PFOS<PFNA<PFOA<<PFBS), higher-doses of these chemicals induced a larger impact.

4.Positive Impact of Nutritional Interventions on Serum Symmetric Dimethylarginine and Creatinine Concentrations in Client-Owned Geriatric Cats.

Hall JA1, MacLeay J2, Yerramilli M3, Obare E3, Yerramilli M3, Schiefelbein H2, Paetau-Robinson I2, Jewell DE2. PLoS One. 2016 Apr 14;11(4):e0153654. doi: 10.1371/journal.pone.0153654.

A prospective study was conducted in client-owned geriatric cats to evaluate the short- term effects of a test food on serum symmetric dimethylarginine (SDMA) and creatinine (Cr) concentrations. Test food contained functional lipids (fish oil), antioxidants (vitamins C and E), L-carnitine, botanicals (vegetables), highly bioavailable protein, and amino acid supplements. Cats (n = 80) were fed either test food or owner's-choice foods (non-nutritionally controlled cohort). Cats were included based on age (≥ 9 years), indoor only, neutered, and free of chronic disease. At baseline, all cats had serum Cr concentrations within the reference interval. Renal function biomarkers and urinalysis results at baseline and after consuming test food or owner's-choice foods for 3 and 6 months were evaluated. Cats consuming test food showed significant decreases in serum Cr and BUN concentrations across time. Overall, cats consuming owner's-choice foods showed significant increases in serum SDMA concentrations at 3 and 6 months compared with baseline (P ≤ 0.