Structure of Fmoc-Asp(OAll)-OH
CAS No.: 146982-24-3
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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Andrews, Emily R ;
Abstract: Metal chelators developed from peptides boast favorable attributes such as low toxicity, ease of synthesis, and high tunabilty to the target metal ion. It is for these reasons that peptides are used for metal sensing and sequestration in the body and environment. Herein, two unique sets of metal targeting peptides are discussed: (1) bifunctional Szeto-Schiller and Kelley peptide probes to signal the presence of and remove labile iron (Fe2+ and Fe3+) in the mitochondria, to mitigate the progression of Ferroptosis and (2) Pb2+ targeting peptides designed to exist in aqueous environments for the removal of toxic lead ions from waterways. These peptides were synthesized manually via solid phase peptide synthesis (SPPS) and determination of impurities and success of synthesis was carried out using analytical high-performance liquid chromatography (HPLC). Aspects of these peptides and their syntheses were explored, with special attention given to membrane lipophilicity, degree of epimerization due to synthetic protocols and protecting groups, and simulated metal complexation structures using computational modeling software. It was determined through these studies that the reagents used for peptide synthesis are heavily residue-dependent, and both the iron and lead (II) targeting peptides have shown promising metal chelation at early stages. Recommendations for further methods for analysis and determination of the lipophilicities of the iron probes are discussed, as well as additional computational studies and paths for sequence optimization for the lead (II) peptides.
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Purchased from AmBeed: 146982-24-3 ; 92954-90-0 ; 103213-32-7 ; 71989-33-8 ; 35661-40-6 ; 14970-87-7 ; 654670-89-0
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| CAS No. : | 146982-24-3 |
| Formula : | C22H21NO6 |
| M.W : | 395.41 |
| SMILES Code : | O=C(O)[C@@H](NC(OCC1C2=C(C3=C1C=CC=C3)C=CC=C2)=O)CC(OCC=C)=O |
| MDL No. : | MFCD00190874 |
| InChI Key : | FBNFRRNBFASDKS-IBGZPJMESA-N |
| Pubchem ID : | 10715692 |
| GHS Pictogram: |
|
| Signal Word: | Warning |
| Hazard Statements: | H315-H319-H335 |
| Precautionary Statements: | P261-P305+P351+P338 |
| Num. heavy atoms | 29 |
| Num. arom. heavy atoms | 12 |
| Fraction Csp3 | 0.23 |
| Num. rotatable bonds | 11 |
| Num. H-bond acceptors | 6.0 |
| Num. H-bond donors | 2.0 |
| Molar Refractivity | 105.21 |
| TPSA ? Topological Polar Surface Area: Calculated from |
101.93 Ų |
| Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.94 |
| Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.16 |
| Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.1 |
| Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.27 |
| Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.23 |
| Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.94 |
| Log S (ESOL):? ESOL: Topological method implemented from |
-3.86 |
| Solubility | 0.0543 mg/ml ; 0.000137 mol/l |
| Class? Solubility class: Log S scale |
Soluble |
| Log S (Ali)? Ali: Topological method implemented from |
-4.97 |
| Solubility | 0.00423 mg/ml ; 0.0000107 mol/l |
| Class? Solubility class: Log S scale |
Moderately soluble |
| Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-5.39 |
| Solubility | 0.00159 mg/ml ; 0.00000403 mol/l |
| Class? Solubility class: Log S scale |
Moderately soluble |
| GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
High |
| BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
No |
| P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
Yes |
| CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
Yes |
| CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
Yes |
| CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
Yes |
| CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
| CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
| Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.47 cm/s |
| Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
| Ghose? Ghose filter: implemented from |
None |
| Veber? Veber (GSK) filter: implemented from |
1.0 |
| Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
| Muegge? Muegge (Bayer) filter: implemented from |
0.0 |
| Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.56 |
| PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
| Brenk? Structural Alert: implemented from |
2.0 alert: heavy_metal |
| Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<2.0 |
| Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
4.15 |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.