Tyropeptin A
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| Category | Enzyme inhibitors |
| Catalog number | BBF-02734 |
| CAS | |
| Molecular Weight | 511.61 |
| Molecular Formula | C28H37N3O6 |
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Description
It is produced by the strain of Kitasatospora sp. MK993-dF2. Tyropeptin A inhibited CHT-L and T-L activity of 20S proteasome with IC50 of 0.10 and 1.5 μg/mL, respectively.
Specification
| Synonyms | Isovaleryl-L-tyrosyl-L-valyl-DL-tyrosinal |
| IUPAC Name | (2S)-2-[[(2S)-3-(4-hydroxyphenyl)-2-(3-methylbutanoylamino)propanoyl]amino]-N-[1-(4-hydroxyphenyl)-3-oxopropan-2-yl]-3-methylbutanamide |
| Canonical SMILES | CC(C)CC(=O)NC(CC1=CC=C(C=C1)O)C(=O)NC(C(C)C)C(=O)NC(CC2=CC=C(C=C2)O)C=O |
| InChI | InChI=1S/C28H37N3O6/c1-17(2)13-25(35)30-24(15-20-7-11-23(34)12-8-20)27(36)31-26(18(3)4)28(37)29-21(16-32)14-19-5-9-22(33)10-6-19/h5-12,16-18,21,24,26,33-34H,13-15H2,1-4H3,(H,29,37)(H,30,35)(H,31,36)/t21?,24-,26-/m0/s1 |
| InChI Key | OSMJFYFZOAVCNP-KLZDYHPHSA-N |
Properties
| Appearance | White Powder |
| Boiling Point | 850.5±65.0°C at 760 mmHg |
| Melting Point | 100-102°C |
| Density | 1.2±0.1 g/cm3 |
Reference Reading
1. [Boronic Acid as a Promising Class of Chemical Entity for Development of Clinical Medicine for Targeted Therapy of Cancer]
Takumi Watanabe, Isao Momose Yakugaku Zasshi. 2022;142(2):145-153. doi: 10.1248/yakushi.21-00173-3.
The first medicine containing the boron element, bortezomib, was approved for clinical use just 18 years ago. The boronic acid substructure in bortezomib serves as an electrophilic functionality with high affinity for hydroxy groups, which are frequently found in catalytic sites of proteolytic enzymes, to create reversible covalent bonds with a slow dissociation rate. Today, boronic acid is considered an important molecule in the medicinal chemistry toolbox, which was promoted by the success of bortezomib and pioneering approaches to use boronic acid in the molecular design of serine protease inhibitors in the 1980s. In this review article, we first provide an overview of the development of bortezomib, and then summarize our achievements to construct boronic acid analogs of tyropeptin A, a naturally occurring proteasome inhibitor, with potent in vivo efficacy. Representative stereoselective synthetic methods of α-aminoboronic acid are also showcased.
2. Tyropeptins, proteasome inhibitors produced by Kitasatospora sp. MK993-dF2
Isao Momose, Takumi Watanabe J Antibiot (Tokyo). 2017 May;70(5):542-550. doi: 10.1038/ja.2017.9. Epub 2017 Feb 15.
Tyropeptins are new proteasome inhibitors isolated from the culture broth of Kitasatospora sp. MK993-dF2. Tyropeptins permeate cell membranes, inhibit intracellular proteasomes and reduce the degradation of ubiquitinated proteins in mammalian cells. We performed structure-based drug design and structure-activity relationship studies on tyropeptin derivatives to obtain valuable information of derivatives. Among the synthesized tyropeptin derivatives, some boronic acid derivatives exhibited potent antitumor effects against human multiple myeloma. In this review, we summarize the discovery of tyropeptins and the development of tyropeptin derivatives.
3. Combined 3D-QSAR, molecular docking and molecular dynamics study on derivatives of peptide epoxyketone and tyropeptin-boronic acid as inhibitors against the β5 subunit of human 20S proteasome
Jianling Liu, Hong Zhang, Zhengtao Xiao, Fangfang Wang, Xia Wang, Yonghua Wang Int J Mol Sci. 2011;12(3):1807-35. doi: 10.3390/ijms12031807. Epub 2011 Mar 9.
An abnormal ubiquitin-proteasome is found in many human diseases, especially in cancer, and has received extensive attention as a promising therapeutic target in recent years. In this work, several in silico models have been built with two classes of proteasome inhibitors (PIs) by using 3D-QSAR, homology modeling, molecular docking and molecular dynamics (MD) simulations. The study resulted in two types of satisfactory 3D-QSAR models, i.e., the CoMFA model (Q(2) = 0.462, R(2) (pred) = 0.820) for epoxyketone inhibitors (EPK) and the CoMSIA model (Q(2) = 0.622, R(2) (pred) = 0.821) for tyropeptin-boronic acid derivatives (TBA). From the contour maps, some key structural factors responsible for the activity of these two series of PIs are revealed. For EPK inhibitors, the N-cap part should have higher electropositivity; a large substituent such as a benzene ring is favored at the C6-position. In terms of TBA inhibitors, hydrophobic substituents with a larger size anisole group are preferential at the C8-position; higher electropositive substituents like a naphthalene group at the C3-position can enhance the activity of the drug by providing hydrogen bond interaction with the protein target. Molecular docking disclosed that residues Thr60, Thr80, Gly106 and Ser189 play a pivotal role in maintaining the drug-target interactions, which are consistent with the contour maps. MD simulations further indicated that the binding modes of each conformation derived from docking is stable and in accord with the corresponding structure extracted from MD simulation overall. These results can offer useful theoretical references for designing more potent PIs.
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Bio Calculators
* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2
* Total Molecular Weight:
g/mol
Tip: Chemical formula is case sensitive. C22H30N4O √ c22h30n40 ╳
