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Fa-Gly-OH

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Category
Other Unnatural Amino Acids
Catalog number
BAT-008866
CAS number
124882-74-2
Molecular Formula
C9H9NO4
Molecular Weight
195.17
Fa-Gly-OH
IUPAC Name
2-[[(E)-3-(furan-2-yl)prop-2-enoyl]amino]acetic acid
Synonyms
(E)-2-(3-(Furan-2-yl)acrylamido)acetic acid; Furanacryloylglycine; Fa Gly OH
Appearance
White to off-white powder
Purity
95%
Density
1.329g/cm3
Melting Point
>215°C (dec.)
Boiling Point
482.8ºC at 760 mmHg
Storage
Store at RT.
InChI
InChI=1S/C9H9NO4/c11-8(10-6-9(12)13)4-3-7-2-1-5-14-7/h1-5H,6H2,(H,10,11)(H,12,13)/b4-3+
InChI Key
XJVSWKBQMAOKAX-ONEGZZNKSA-N
Canonical SMILES
C1=COC(=C1)C=CC(=O)NCC(=O)O
1. Evaluation of the permeation characteristics of a model opioid peptide, H-Tyr-D-Ala-Gly-Phe-D-Leu-OH (DADLE), and its cyclic prodrugs across the blood-brain barrier using an in situ perfused rat brain model
Weiqing Chen, Jerry Z Yang, Rikke Andersen, Lisbeth H Nielsen, Ronald T Borchardt J Pharmacol Exp Ther. 2002 Nov;303(2):849-57. doi: 10.1124/jpet.102.037143.
The permeation characteristics of a model opioid peptide, H-Tyr-D-Ala-Gly-Phe-D-Leu-OH (DADLE), and its cyclic prodrugs [acyloxyalkoxy-based cyclic prodrug of DADLE (AOA-DADLE), coumarinic acid-based cyclic prodrug of DADLE (CA-DALE), and oxymethyl-modified coumarinic acid-based cyclic prodrug of DADLE (OMCA-DADLE)] across the blood-brain barrier (BBB) were determined using an in situ perfused rat brain model. The rat brains were perfused with Krebs-bicarbonate buffer containing test compounds in the absence or presence of a specific P-glycoprotein inhibitor (GF-120918). Brain samples were collected after perfusion and processed by a capillary depletion method. After liquid phase extraction with acetonitrile, samples were analyzed using high-performance liquid chromatography with tandem mass spectrometric detection. Linear uptake kinetics of DADLE and its cyclic prodrugs was observed within the range of 60 to 240 s of perfusion. The apparent permeability coefficient (P(app)) of DADLE across the BBB was very low (<10(-7) cm/s), probably due to its unfavorable physicochemical properties (e.g., charge, hydrophilicity, and high hydrogen-bonding potential). All three cyclic prodrugs, however, also exhibited low membrane permeation (P(app) <10(-7) cm/s) in spite of their more favorable physicochemical properties (e.g., no charge, high hydrophobicity, and low hydrogen-bonding potential). Inclusion of GF-120918 (10 microM) in the perfusates fully inhibited the P-gp activity in the BBB and dramatically increased the P(app) values of AOA-DADLE, CA-DADLE, and OMCA-DADLE by approximately 50-, 460-, and 170-fold, respectively. In contrast, GF-120918 had no effect on the P(app) value of DADLE. In addition, the observed bioconversions of the prodrugs to DADLE in the rat brains after 240-s perfusion were very low (5.1% from AOA-DADLE, 0.6% from CA-DADLE, and 0.2% from OMCA-DADLE), which was consistent with the in vitro bioconversion rates determined previously in rat brain homogenates.
2. Protein expression profile of HT-29 human colon cancer cells after treatment with a cytotoxic daunorubicin-GnRH-III derivative bioconjugate
Verena Natalie Schreier, Lilla Pethő, Erika Orbán, Andreas Marquardt, Brindusa Alina Petre, Gábor Mező, Marilena Manea PLoS One. 2014 Apr 9;9(4):e94041. doi: 10.1371/journal.pone.0094041. eCollection 2014.
Targeted delivery of chemotherapeutic agents is a new approach for the treatment of cancer, which provides increased selectivity and decreased systemic toxicity. We have recently developed a promising drug delivery system, in which the anticancer drug daunorubicin (Dau) was attached via oxime bond to a gonadotropin-releasing hormone-III (GnRH-III) derivative used as a targeting moiety (Glp-His-Trp-Lys(Ac)-His-Asp-Trp-Lys(Da = Aoa)-Pro-Gly-NH2; Glp = pyroglutamic acid, Ac = acetyl; Aoa = aminooxyacetyl). This bioconjugate exerted in vitro cytostatic/cytotoxic effect on human breast, prostate and colon cancer cells, as well as significant in vivo tumor growth inhibitory effect on colon carcinoma bearing mice. In our previous studies, H-Lys(Dau = Aoa)-OH was identified as the smallest metabolite produced in the presence of rat liver lysosomal homogenate, which was able to bind to DNA in vitro. To get a deeper insight into the mechanism of action of the bioconjugate, changes in the protein expression profile of HT-29 human colon cancer cells after treatment with the bioconjugate or free daunorubicin were investigated by mass spectrometry-based proteomics. Our results indicate that several metabolism-related proteins, molecular chaperons and proteins involved in signaling are differently expressed after targeted chemotherapeutic treatment, leading to the conclusion that the bioconjugate exerts its cytotoxic action by interfering with multiple intracellular processes.
3. In Vivo Tumor Growth Inhibition and Antiangiogenic Effect of Cyclic NGR Peptide-Daunorubicin Conjugates Developed for Targeted Drug Delivery
Andrea Angelo Pierluigi Tripodi, Ivan Ranđelović, Beáta Biri-Kovács, Bálint Szeder, Gábor Mező, József Tóvári Pathol Oncol Res. 2020 Jul;26(3):1879-1892. doi: 10.1007/s12253-019-00773-3. Epub 2019 Dec 9.
Among various homing devices, peptides containing the NGR tripeptide sequence represent a promising approach to selectively recognize CD13 receptor isoforms on the surface of tumor cells. They have been successfully used for the delivery of various chemotherapeutic drugs to tumor vessels. Here, we report on the murine plasma stability, in vitro and in vivo antitumor activity of our recently described bioconjugates containing daunorubicin as payload. Furthermore, CD13 expression of KS Kaposi's Sarcoma cell line and HT-29 human colon carcinoma cell line was investigated. Flow cytometry studies confirm the fast cellular uptake resulting in the rapid delivery of the active metabolite Dau = Aoa-Gly-OH to tumor cells. The increased in vitro antitumor effect might be explained by the faster rearrangement from NGR to isoDGR in case of conjugate 2 (Dau = Aoa-GFLGK(c[NleNGRE]-GG)-NH2) in comparison with conjugate 1 (Dau = Aoa-GFLGK(c[KNGRE]-GG)-NH2). Nevertheless, results indicated that both conjugates showed significant effect on inhibition of proliferation in the primary tumor and also on blood vessel formation making them a potential candidate for targeting angiogenesis processes in tumors where CD13 and integrins are involved.
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