Matlystatin B
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| Category | Enzyme inhibitors |
| Catalog number | BBF-02309 |
| CAS | 140923-32-6 |
| Molecular Weight | 440.58 |
| Molecular Formula | C22H40N4O5 |
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Description
It is produced by the strain of Actinomadura atramentaria. It's a Type V collagenase inhibitor. It can inhibit type IV collagenase and type I collagenase with ID50 (μmol/L) of 1.43 and 1.2, respectively. It has anti-gram-positive bacteria effect.
Specification
| Synonyms | 1(2H)-Pyridazinebutanamide, tetrahydro-N-hydroxy-6-[[[2-methyl-1-(1-oxopropyl)butyl]amino]carbonyl]-g-oxo-b-pentyl-, [6S-[1(S*),6R*(1R*,2R*)]]-; Matlystatin B1 |
| IUPAC Name | (3S)-2-[(2R)-2-[2-(hydroxyamino)-2-oxoethyl]heptanoyl]-N-[(3S,4S)-3-methyl-5-oxoheptan-4-yl]diazinane-3-carboxamide |
| Canonical SMILES | CCCCCC(CC(=O)NO)C(=O)N1C(CCCN1)C(=O)NC(C(C)CC)C(=O)CC |
| InChI | InChI=1S/C22H40N4O5/c1-5-8-9-11-16(14-19(28)25-31)22(30)26-17(12-10-13-23-26)21(29)24-20(15(4)6-2)18(27)7-3/h15-17,20,23,31H,5-14H2,1-4H3,(H,24,29)(H,25,28)/t15-,16+,17-,20-/m0/s1 |
| InChI Key | IWWYEUSBHSDVOX-CLWJZODNSA-N |
Properties
| Appearance | White Hygroscopic Powder |
| Antibiotic Activity Spectrum | Gram-positive bacteria |
| Melting Point | 69-72°C |
| Density | 1.107±0.06 g/cm3 (Predicted) |
| Solubility | Soluble in Ethanol |
Reference Reading
1. Matlystatins, new inhibitors of type IV collagenases from Actinomadura atramentaria. IV. Synthesis and structure-activity relationships of matlystatin B and its stereoisomers
K Tamaki, S Kurihara, T Oikawa, K Tanzawa, Y Sugimura J Antibiot (Tokyo). 1994 Dec;47(12):1481-92. doi: 10.7164/antibiotics.47.1481.
The first total synthesis of matlystatin B (1a), a low molecular weight inhibitor of type IV collagenases, was accomplished, and its absolute configuration was unambiguously determined. Furthermore, ten stereoisomers of 1a were synthesized, and the inhibition of the 92 kDa type IV collagenase and of other metalloproteinases by each stereoisomer was investigated.
2. Warhead biosynthesis and the origin of structural diversity in hydroxamate metalloproteinase inhibitors
Franziska Leipoldt, Javier Santos-Aberturas, Dennis P Stegmann, Felix Wolf, Andreas Kulik, Rodney Lacret, Désirée Popadić, Daniela Keinhörster, Norbert Kirchner, Paulina Bekiesch, Harald Gross, Andrew W Truman, Leonard Kaysser Nat Commun. 2017 Dec 6;8(1):1965. doi: 10.1038/s41467-017-01975-6.
Metalloproteinase inhibitors often feature hydroxamate moieties to facilitate the chelation of metal ions in the catalytic center of target enzymes. Actinonin and matlystatins are potent metalloproteinase inhibitors that comprise rare N-hydroxy-2-pentyl-succinamic acid warheads. Here we report the identification and characterization of their biosynthetic pathways. By gene cluster comparison and a combination of precursor feeding studies, heterologous pathway expression and gene deletion experiments we are able to show that the N-hydroxy-alkyl-succinamic acid warhead is generated by an unprecedented variation of the ethylmalonyl-CoA pathway. Moreover, we present evidence that the remarkable structural diversity of matlystatin congeners originates from the activity of a decarboxylase-dehydrogenase enzyme with high similarity to enzymes that form epoxyketones. We further exploit this mechanism to direct the biosynthesis of non-natural matlystatin derivatives. Our work paves the way for follow-up studies on these fascinating pathways and allows the identification of new protease inhibitors by genome mining.
3. Synthesis and structure-activity relationships of gelatinase inhibitors derived from matlystatins
K Tamaki, K Tanzawa, S Kurihara, T Oikawa, S Monma, K Shimada, Y Sugimura Chem Pharm Bull (Tokyo). 1995 Nov;43(11):1883-93. doi: 10.1248/cpb.43.1883.
To investigate a series of new inhibitors of gelatinases based on matlystatin B (1b), extensive structure-activity relationship studies were performed. The new derivatives were evaluated in vitro for the ability to inhibit gelatinases. The inhibitory activities against thermolysin were also assayed to test the compounds' selectivity. Among the compounds modified at the P'3 moiety, the N-methylamide derivative 5 g was virtually twice as effective on gelatinase B as the parent compound 1b (5g, IC50 = 0.27 microM vs. 1b, IC50 = 0.57 microM). Other derivatives, including 1) esters 7a and 7b having the ester portions P'2 and P'3, 2) the cyclic amino acids, L-proline or L-pipecolinic acid (13a and 13b) bearing P'2, and 3) compounds 29a and 29b representing an attachment of the pentyl side chain at C3' (P'1 side chain) instead of C2', all showed decreased potencies. The key discovery was the observation that the introduction of a nonyl group at the P'1 position yielded a compound (31f, IC50 = 0.0012 microM) with high inhibitory activity against gelatinases and high selectivity over thermolysin. This result suggested that the S'1 subsites of the gelatinases have a locally deep hydrophobic structure, since on the basis of the optimum inhibitory activity in the alkyl series, the nonyl group seems to fit best into this hydrophobic pocket. Thus 31f exhibited a 475-fold more potent inhibitory activity than 1b towards gelatinase B.
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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 ╳
