FR-901451
* Please be kindly noted products are not for therapeutic use. We do not sell to patients.
| Category | Enzyme inhibitors |
| Catalog number | BBF-03569 |
| CAS | |
| Molecular Weight | 1284.37 |
| Molecular Formula | C61H81N13O18 |
Online Inquiry
Description
It is originally isolated from Flexibacter sp. No. 758. FR-901451 had inhibitory activity against HLE with ID50 of 2.3 X 10-7 mol/L. And it also has inhibitory effects on PPE, chymosin and proteinase.
Specification
| IUPAC Name | (1S,4S,7S,12S,13S,16S,19S,22S,28S,31S,38S)-13-[[(2S,3R)-2-amino-3-hydroxybutanoyl]amino]-22-benzyl-4-(1H-indol-2-ylmethyl)-12-methyl-16-(2-methylpropyl)-3,6,10,14,17,20,23,29,34,36,40,46-dodecaoxo-11,33-dioxa-2,5,15,18,21,24,30,37,41,47-decazatetracyclo[17.16.10.27,31.024,28]heptatetracontane-38-carboxylic acid |
| Canonical SMILES | CC1C(C(=O)NC(C(=O)NC2CCCCNC(=O)CC(NC(=O)C3CC(=O)OCC(C(=O)NC(CCC(=O)O1)C(=O)NC(C(=O)N3)CC4=CC5=CC=CC=C5N4)NC(=O)C6CCCN6C(=O)C(NC2=O)CC7=CC=CC=C7)C(=O)O)CC(C)C)NC(=O)C(C(C)O)N |
| InChI | InChI=1S/C61H81N13O18/c1-30(2)23-39-53(81)65-37-17-10-11-21-63-46(76)27-43(61(89)90)71-55(83)41-28-48(78)91-29-44(72-57(85)45-18-12-22-74(45)60(88)42(70-51(37)79)24-33-13-6-5-7-14-33)56(84)66-38(19-20-47(77)92-32(4)50(59(87)69-39)73-58(86)49(62)31(3)75)52(80)67-40(54(82)68-41)26-35-25-34-15-8-9-16-36(34)64-35/h5-9,13-16,25,30-32,37-45,49-50,64,75H,10-12,17-24,26-29,62H2,1-4H3,(H,63,76)(H,65,81)(H,66,84)(H,67,80)(H,68,82)(H,69,87)(H,70,79)(H,71,83)(H,72,85)(H,73,86)(H,89,90)/t31-,32+,37+,38+,39+,40+,41+,42+,43+,44+,45+,49+,50+/m1/s1 |
| InChI Key | OBJRDBYSSAEARM-WSFPPIIISA-N |
Properties
| Appearance | White Powder |
| Boiling Point | 1778.5±65.0°C at 760 mmHg |
| Melting Point | 243-245°C |
| Density | 1.4±0.1 g/cm3 |
Reference Reading
1. Uncovering a Subtype of Microviridins via the Biosynthesis Study of FR901451
Tingting Wang, Xiaotong Wang, Haowen Zhao, Liujie Huo, Chengzhang Fu ACS Chem Biol. 2022 Dec 16;17(12):3489-3498. doi: 10.1021/acschembio.2c00688. Epub 2022 Nov 14.
Microviridins are a class of ribosomally synthesized and post-translationally modified peptides originally discovered from cyanobacteria, featured by intramolecular ω-ester and ω-amide bonds catalyzed by two ATP-grasp ligases. In this study, 104 biosynthetic gene clusters of microviridins from Bacteroidetes were bioinformatically analyzed, which unveiled unique features of precursor peptides. The analysis of core peptides revealed a microviridin-like biosynthetic gene cluster from Chitinophagia japonensis DSM13484 consisting of two potential precursors ChiA1 and ChiA2. Unexpectedly, the core peptide sequence of ChiA1 is consistent with the backbone of the elastase-inhibiting peptide FR901451, while ChiA2 is likely to be a precursor of an unknown product. However, an unusual C-terminal follower cleavage compared to the previously known microviridin pathways was observed and found to be dispensable for other modifications. To confirm the biosynthetic origin of FR901451, ATP-grasp ligases ChiC and ChiB were biochemically characterized to be responsible for the intramolecular ester and amide bond formation, respectively. In vitro reconstitution of the pathway showed the three-fold dehydrations of ChiA1 while unusual four-fold dehydrations were observed for ChiA2. Furthermore, in vivo gene coexpression facilitated the production of chitinoviridin A1 (FR901451) and two novel microviridin-class compounds chitinoviridin A2A and chitinoviridin A2B, with an extra macrolactone ring. All of these peptides showed potent inhibitory effects against elastase and chymotrypsin independently.
2. Structure of the complex of porcine pancreatic elastase with a trimacrocyclic peptide inhibitor FR901451
Takayoshi Kinoshita, Tomoya Kitatani, Masaichi Warizaya, Toshiji Tada Acta Crystallogr Sect F Struct Biol Cryst Commun. 2005 Sep 1;61(Pt 9):808-11. doi: 10.1107/S1744309105026047. Epub 2005 Aug 31.
Porcine pancreatic elastase (PPE) resembles the attractive drug target leukocyte elastase, which has the ability to degrade connective tissue in the body. The crystal structure of PPE complexed with a novel trimacrocyclic peptide inhibitor, FR901451, was solved at 1.9 A resolution. The inhibitor occupied the subsites S3 through S3' of PPE and induced conformational changes in the side chains of Arg64 and Arg226, which are located at the edges of the substrate-binding cleft. Structural comparison of five PPE-inhibitor complexes, including the FR901451 complex and non-ligated PPE, reveals that the residues forming the S2, S1, S1' and S2' subsites in the cleft are rigid, but the two arginine residues playing a part in the S3 and S3' subsites are flexible. Structural comparison of PPE with human leukocyte elastase (HLE) implies that the inhibitor binds to HLE in a similar manner to the FR901451-PPE complex. This structural insight may help in the design of potent elastase inhibitors.
3. FR901451, a novel inhibitor of human leukocyte elastase from Flexibacter sp. II. Pharmacological effect of FR901451
T Fujita, Y Shinguh, A Yamazaki, K Nakahara, M Okamoto, M Okuhara J Antibiot (Tokyo). 1994 Dec;47(12):1365-8. doi: 10.7164/antibiotics.47.1365.
Intratracheal (i.t.) or intravenous (i.v.) administration of FR901451, a potent inhibitor of human leukocyte elastase (HLE) prevented HLE-induced lung hemorrhage in hamsters with ED50 values of 10.5 micrograms/site and 8.1 mg/kg, respectively. alpha 1-Antitrypsin (alpha 1-AT) also showed inhibitory effect in this model. However, the ED50 value by i.t. injection of FR901451 was 20-fold lower than that of alpha 1-AT. Moreover, FR901451 i.t. significantly modulated porcine pancreas elastase (PPE)-induced changes of the respiratory mechanics in hamsters. The ED50 values were 529 micrograms/site and 244 micrograms/site, which were expressed by static lung compliance (Cst) and vital capacity (VC) of the lungs, respectively. These results suggest that FR901451 could be clinically useful agent for the treatment of the destructive lung disease such as pulmonary emphysema.
Recommended Products
| BBF-03754 | Castanospermine | Inquiry |
| BBF-01826 | Deoxymannojirimycin | Inquiry |
| BBF-01829 | Deoxynojirimycin | Inquiry |
| BBF-05862 | Epirubicin | Inquiry |
| BBF-02642 | Lactonamycin | Inquiry |
| BBF-01825 | Loganin | Inquiry |
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 ╳
