3-Benzothienyl-L-alanine
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3-Benzothienyl-L-alanine

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Category
L-Amino Acids
Catalog number
BAT-007825
CAS number
72120-71-9
Molecular Formula
C11H11NO2S
Molecular Weight
221.28
3-Benzothienyl-L-alanine
IUPAC Name
(2S)-2-amino-3-(1-benzothiophen-3-yl)propanoic acid
Synonyms
3-L-Ala(3-benzothienyl)-OH; 3-Benzo[b]thiophen-3-yl-L-alanine; L-3-Benzothienylalanine; (S)-2-Amino-3-(benzo[b]thiophen-3-yl)propanoic acid; 3-(1-Benzothiophen-3-Yl)-L-Alanine; 3-(3-Benzo(b)thienyl)alanine; 3-BENZO[B]THIOPHEN-3-YL-L-ALANINE; (2S)-2-amino-3-(1-benzothiophen-3-yl)propanoic acid; D-3-(3-Benzothienyl)alanine; 3-(3-benzo[b]thienyl)alanine
Related CAS
111139-55-0 (D-isomer)
Appearance
Almost white powder
Purity
≥ 98.5% (assay)
Density
1.374±0.06 g/cm3 (Predicted)
Melting Point
248-250 °C (dec.)
Boiling Point
416.7±35.0 °C (Predicted)
Storage
Store at 2-8 °C
InChI
InChI=1S/C11H11NO2S/c12-9(11(13)14)5-7-6-15-10-4-2-1-3-8(7)10/h1-4,6,9H,5,12H2,(H,13,14)/t9-/m0/s1
InChI Key
GAUUPDQWKHTCAX-VIFPVBQESA-N
Canonical SMILES
C1=CC=C2C(=C1)C(=CS2)CC(C(=O)O)N

3-Benzothienyl-L-alanine (BTAA) is a versatile and valuable compound with applications across several key fields. One of the primary applications is in medicinal chemistry. BTAA has shown promise as a building block for the synthesis of bioactive molecules. Its unique heterocyclic structure, which combines both benzothiophene and amino acid moieties, allows for the design of novel pharmaceutical agents with potential therapeutic benefits. Researchers have been investigating its use in developing new drugs with improved efficacy and selectivity, targeting diseases such as cancer, bacterial infections, and neurological disorders. By incorporating BTAA into drug design, scientists aim to exploit its structural features to enhance drug-receptor interactions, stability, and bioavailability.

Another significant application of BTAA is in the realm of organic synthesis. The compound serves as a valuable intermediate in the creation of complex organic molecules. Its dual-functionality offers chemists the ability to perform a wide range of chemical transformations, from nucleophilic substitutions to cyclizations, enabling the construction of highly diversified molecular architectures. For instance, BTAA can be employed in the synthesis of various heterocyclic compounds, which are often key components in pharmaceuticals, agrochemicals, and material science. Its adaptability and reactivity make it a staple in synthetic organic laboratories, where it is utilized to streamline the production of advanced molecular entities.

In the field of materials science, 3-Benzothienyl-L-alanine also finds notable applications. As an organic compound with unique electronic and structural properties, BTAA is being researched for its potential in creating novel materials with specialized functionalities. One promising area is in the development of organic semiconductors. These materials are essential for the next generation of electronic devices, such as organic light-emitting diodes (OLEDs), organic photovoltaics (OPVs), and field-effect transistors (OFETs). BTAA’s conjugated system and ability to facilitate charge transfer make it a candidate for enhancing the performance of these devices. Moreover, its incorporation into polymeric materials could lead to the creation of new thermally stable and electroluminescent materials.

Finally, BTAA has important applications in analytical chemistry, particularly in the realm of biosensors and detection methods. The compound's structural versatility makes it suitable for developing selective and sensitive probes for detecting various biological analytes. For example, BTAA-derived sensors can be tailored to detect specific biomolecules, such as enzymes, proteins, or nucleic acids, with high specificity and sensitivity. This capability is crucial for early diagnosis and monitoring of diseases, environmental monitoring, and food safety testing. The incorporation of BTAA into sensor systems can enhance the detection limits and response times, leading to more accurate and reliable analytical tools. This application underscores BTAA’s potential in advancing the field of diagnostic and analytical technologies.

1. Expanding the Scope of Orthogonal Translation with Pyrrolysyl-tRNA Synthetases Dedicated to Aromatic Amino Acids
Hsueh-Wei Tseng, Tobias Baumann, Huan Sun, Yane-Shih Wang, Zoya Ignatova, Nediljko Budisa Molecules. 2020 Sep 25;25(19):4418. doi: 10.3390/molecules25194418.
In protein engineering and synthetic biology, Methanosarcina mazei pyrrolysyl-tRNA synthetase (MmPylRS), with its cognate tRNAPyl, is one of the most popular tools for site-specific incorporation of non-canonical amino acids (ncAAs). Numerous orthogonal pairs based on engineered MmPylRS variants have been developed during the last decade, enabling a substantial genetic code expansion, mainly with aliphatic pyrrolysine analogs. However, comparatively less progress has been made to expand the substrate range of MmPylRS towards aromatic amino acid residues. Therefore, we set to further expand the substrate scope of orthogonal translation by a semi-rational approach; redesigning the MmPylRS efficiency. Based on the randomization of residues from the binding pocket and tRNA binding domain, we identify three positions (V401, W417 and S193) crucial for ncAA specificity and enzyme activity. Their systematic mutagenesis enabled us to generate MmPylRS variants dedicated to tryptophan (such as β-(1-Azulenyl)-l-alanine or 1-methyl-l-tryptophan) and tyrosine (mainly halogenated) analogs. Moreover, our strategy also significantly improves the orthogonal translation efficiency with the previously activated analog 3-benzothienyl-l-alanine. Our study revealed the engineering of both first shell and distant residues to modify substrate specificity as an important strategy to further expand our ability to discover and recruit new ncAAs for orthogonal translation.
2. Probing the Active Site of Deubiquitinase USP30 with Noncanonical Tryptophan Analogues
Han-Kai Jiang, Yi-Hui Wang, Jui-Hung Weng, Prashant Kurkute, Chien-Lung Li, Man-Nee Lee, Pei-Jung Chen, Hsueh-Wei Tseng, Ming-Daw Tsai, Yane-Shih Wang Biochemistry. 2020 Jun 23;59(24):2205-2209. doi: 10.1021/acs.biochem.0c00307. Epub 2020 Jun 8.
Methanosarcina mazei pyrrolysyl-tRNA synthetase (PylRS) and its cognate tRNA have been evolved to generate genetically encoded noncanonical amino acids (ncAAs). Use of tryptophan (Trp) analogues with pyrrole ring modification for their spatial and polarity tuning in enzyme activity and substrate specificity is still limited. Herein, we report the application of an evolved PylRS, FOWRS2, for efficient incorporation of five Trp analogues into the deubiquitinase USP30 to decipher the role of W475 for diubiquitin selectivity. Structures of the five FOWRS-C/Trp analogue complexes at 1.7-2.5 Å resolution showed multiple ncAA binding modes. The W475 near the USP30 active site was replaced with Trp analogues, and the effect on the activity as well as the selectivity toward diubiquitin linkage types was examined. It was found that the Trp analogue with a formyl group attached to the nitrogen atom of the indole ring led to an improved activity of USP30 likely due to enhanced polar interactions and that another Trp analogue, 3-benzothienyl-l-alanine, induced a unique K6-specificity. Collectively, genetically encoded noncanonical Trp analogues by evolved PylRS·tRNACUAPyl pair unravel the spatial role of USP30-W475 in its diubiquitin selectivity.
3. Discovery of a Cyclic Cell-Penetrating Peptide with Improved Endosomal Escape and Cytosolic Delivery Efficiency
Marina Buyanova, Ashweta Sahni, Rui Yang, Amar Sarkar, Heba Salim, Dehua Pei Mol Pharm. 2022 May 2;19(5):1378-1388. doi: 10.1021/acs.molpharmaceut.1c00924. Epub 2022 Apr 11.
Cyclic cell-penetrating peptide 12 (CPP12) is highly efficient for the cytosolic delivery of a variety of cargo molecules into mammalian cells in vitro and in vivo. However, its cytosolic entry efficiency is substantially reduced at lower concentrations or in the presence of serum proteins. In this study, CPP12 analogs were prepared by replacing its hydrophobic residues with amino acids of varying hydrophobicity and evaluated for cellular entry. Substitution of l-3-benzothienylalanine (Bta) for l-2-naphthylalanine (Nal) resulted in CPP12-2, which exhibits up to 3.8-fold higher cytosolic entry efficiency than CPP12, especially at low CPP concentrations; thanks to improved endosomal escape efficiency. CPP12-2 is well suited for the cytosolic delivery of highly potent cargos to achieve biological activity at low concentrations.
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