Fmoc-D-Val-OH | N-protective Amino Acid

Abstract: Lys ubiquitination is catalysed by E3 ubiquitin ligases and is central to the regulation of protein stability and cell signalling in normal and disease states. There are gaps in our understanding of E3 mechanisms, and here we use protein semisynthesis, chemical rescue, microscale thermophoresis and other biochemical approaches to dissect the role of catalytic base/acid function and conformational interconversion in HECT-domain E3 catalysis. We demonstrate that there is plasticity in the use of the terminal side chain or backbone carboxylate for proton transfer in HECT E3 ubiquitin ligases reactions, with yeast Rsp5 orthologues appearing to be possible evolutionary intermediates. We also show that the HECT-domain ubiquitin covalent intermediate appears to eject the E2 conjugating enzyme, promoting catalytic turnover. These fndings provide key mechanistic insights into how protein ubiquitination occurs and provide a framework for understanding E3 functions and regulation.

Purchased from AmBeed: 84624-17-9 ; 121343-82-6 ; 136083-57-3 ; 1007840-62-1

Product Details of [ 84624-17-9 ]

CAS No. :	84624-17-9
Formula :	C₂₀H₂₁NO₄
M.W :	339.39
SMILES Code :	C(=O)(OCC2C1=CC=CC=C1C3=CC=CC=C23)N[C@H](C(C)C)C(=O)O
Synonyms :	Fmoc-D-Val-OH
MDL No. :	MFCD00062953
InChI Key :	UGNIYGNGCNXHTR-GOSISDBHSA-N
Pubchem ID :	1549479

Safety of [ 84624-17-9 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H332-H335
Precautionary Statements:	P261-P280-P305+P351+P338

Computational Chemistry of [ 84624-17-9 ] Show Less

Physicochemical Properties

Num. heavy atoms	25
Num. arom. heavy atoms	12
Fraction Csp3	0.3
Num. rotatable bonds	7
Num. H-bond acceptors	4.0
Num. H-bond donors	2.0
Molar Refractivity	94.79
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	75.63 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	2.45
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	4.02
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	3.63
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	2.78
Log P_o/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	3.15
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	3.21

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-4.37
Solubility	0.0145 mg/ml ; 0.0000427 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Moderately soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-5.31
Solubility	0.00166 mg/ml ; 0.00000489 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Moderately soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-5.31
Solubility	0.00165 mg/ml ; 0.00000485 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Moderately soluble

Pharmacokinetics

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	Yes
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) and tested on 415 molecules (test set) 10-fold CV: ACC=0.72 / AUC=0.77 External: ACC=0.88 / AUC=0.94	No
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.83 / AUC=0.90 External: ACC=0.84 / AUC=0.91	Yes
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.80 / AUC=0.86 External: ACC=0.80 / AUC=0.87	No
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	Yes
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) and tested on 1068 molecules (test set) 10-fold CV: ACC=0.79 / AUC=0.85 External: ACC=0.81 / AUC=0.87	No
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) and tested on 2579 molecules (test set) 10-fold CV: ACC=0.77 / AUC=0.85 External: ACC=0.78 / AUC=0.86	No
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-5.52 cm/s

Druglikeness

Lipinski? Lipinski (Pfizer) filter: implemented from Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev. MW ≤ 500 MLOGP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5	0.0
Ghose? Ghose filter: implemented from Ghose AK. et al. 1999 J. Comb. Chem. 160 ≤ MW ≤ 480 -0.4 ≤ WLOGP ≤ 5.6 40 ≤ MR ≤ 130 20 ≤ atoms ≤ 70	None
Veber? Veber (GSK) filter: implemented from Veber DF. et al. 2002 J. Med. Chem. Rotatable bonds ≤ 10 TPSA ≤ 140	0.0
Egan? Egan (Pharmacia) filter: implemented from Egan WJ. et al. 2000 J. Med. Chem. WLOGP ≤ 5.88 TPSA ≤ 131.6	0.0
Muegge? Muegge (Bayer) filter: implemented from Muegge I. et al. 2001 J. Med. Chem. 200 ≤ MW ≤ 600 -2 ≤ XLOGP ≤ 5 TPSA ≤ 150 Num. rings ≤ 7 Num. carbon > 4 Num. heteroatoms > 1 Num. rotatable bonds ≤ 15 H-bond acc. ≤ 10 H-bond don. ≤ 5	0.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.56

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	0.0 alert: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<1.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12'782'590 molecules and tested on 40 external molecules (r² = 0.94)	3.78

Application In Synthesis of [ 84624-17-9 ]

* 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.

Downstream synthetic route of [ 84624-17-9 ]

[ 84624-17-9 ] Synthesis Path-Downstream 1~54

1
[ 35661-60-0 ]
[ 35661-39-3 ]
[ 104091-08-9 ]
[ 84624-17-9 ]
Fmoc-D-Trp [ No CAS ]
(R)-4-[(R)-2-Amino-3-(1H-indol-3-yl)-propionylamino]-4-{(S)-1-[(R)-1-((S)-1-hydrazinocarbonyl-3-methyl-butylcarbamoyl)-2-methyl-propylcarbamoyl]-ethylcarbamoyl}-butyric acid tert-butyl ester [ No CAS ]

References: [1]Journal of Medicinal Chemistry,1992,vol. 35,p. 2139 - 2142.

2
[ 35661-60-0 ]
[ 104091-08-9 ]
[ 84624-17-9 ]
[ 147-85-3 ]
Fmoc-D-Trp [ No CAS ]
(R)-4-[(R)-2-Amino-3-(1H-indol-3-yl)-propionylamino]-5-{(S)-2-[(R)-1-((S)-1-hydrazinocarbonyl-3-methyl-butylcarbamoyl)-2-methyl-propylcarbamoyl]-pyrrolidin-1-yl}-5-oxo-pentanoic acid tert-butyl ester [ No CAS ]

References: [1]Journal of Medicinal Chemistry,1992,vol. 35,p. 2139 - 2142.

3
[ 71989-33-8 ]
[ 104091-08-9 ]
[ 84624-17-9 ]
pentanedioic acid mono-(2-{ethyl-[4-(4-nitrophenylazo)-phenyl]amino}-ethyl) ester [ No CAS ]
2-(3-tert-butoxy-2-{4-tert-butoxycarbonyl-2-[4-(2-{ethyl-[4-(4-nitro-phenylazo)-phenyl]-amino}-ethoxycarbonyl)-butyrylamino]-butyrylamino}-propionylamino)-3-methyl-butyric acid [ No CAS ]

References: [1]Chemistry - A European Journal,2002,vol. 8,p. 1300 - 1309.

4
[ 1160862-48-5 ]
[ 35661-38-2 ]
[ 35661-60-0 ]
[ 104091-08-9 ]
[ 84624-17-9 ]
Fmoc-D-Tyr(O-tBu)-OH [ No CAS ]
N-FMOC-O-tert-butyl-D-threonine [ No CAS ]
C₃₆H₅₆N₈O₁₁ [ No CAS ]

References: [1]Journal of the American Chemical Society,2009,vol. 131,p. 7917 - 7927.

5
[ 1160862-48-5 ]
[ 35661-38-2 ]
[ 35661-60-0 ]
[ 104091-08-9 ]
[ 84624-17-9 ]
Fmoc-D-Tyr(O-tBu)-OH [ No CAS ]
N-α-[(9H-fluoren-9-ylmethoxy)carbonyl]-N^G-(2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl)-D-arginine [ No CAS ]
[ 1160862-39-4 ]

References: [1]Journal of the American Chemical Society,2009,vol. 131,p. 7917 - 7927.

6
[ 1160862-48-5 ]
[ 35661-38-2 ]
[ 35661-60-0 ]
[ 104091-08-9 ]
[ 84624-17-9 ]
N-FMOC-O-tert-butyl-D-threonine [ No CAS ]
N-α-[(9H-fluoren-9-ylmethoxy)carbonyl]-N^G-(2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl)-D-arginine [ No CAS ]
C₃₃H₅₉N₁₁O₁₀ [ No CAS ]

References: [1]Journal of the American Chemical Society,2009,vol. 131,p. 7917 - 7927.

7
[ 1160862-48-5 ]
[ 35661-38-2 ]
[ 104091-08-9 ]
[ 84624-17-9 ]
Fmoc-D-Tyr(O-tBu)-OH [ No CAS ]
N-FMOC-O-tert-butyl-D-threonine [ No CAS ]
N-α-[(9H-fluoren-9-ylmethoxy)carbonyl]-N^G-(2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl)-D-arginine [ No CAS ]
C₃₆H₅₇N₁₁O₁₁ [ No CAS ]

References: [1]Journal of the American Chemical Society,2009,vol. 131,p. 7917 - 7927.

8
[ 353491-47-1 ]
[ 67-56-1 ]
[ 1730-89-8 ]
[ 178924-05-5 ]
[ 68858-20-8 ]
[ 118904-37-3 ]
[ 71989-35-0 ]
[ 109425-55-0 ]
[ 71989-31-6 ]
[ 84624-17-9 ]
(4S)-MeHex-D-Val-Thr(tBu)-Val-D-Val-D-Pro-Orn(Boc)-D-aIle-D-Dpr(H-Phe-(Z)Dhb-Val)(Me)-D-aIle-D-Val-OH [ No CAS ]

References: [1]European Journal of Organic Chemistry,2010,p. 2536 - 2543.

9
[ 353491-47-1 ]
[ 1730-89-8 ]
[ 178924-05-5 ]
[ 68858-20-8 ]
[ 118904-37-3 ]
[ 71989-35-0 ]
[ 109425-55-0 ]
[ 71989-31-6 ]
[ 84624-17-9 ]
(4S)-MeHex-D-Val-Thr(tBu)-Val-D-Val-D-Pro-Orn(Boc)-D-aIle-D-Dpr(H-Phe-(Z)Dhb-Val)-D-aIle-D-Val-OH [ No CAS ]

References: [1]European Journal of Organic Chemistry,2010,p. 2536 - 2543.

10
[ 1730-89-8 ]
[ 178924-05-5 ]
[ 68858-20-8 ]
[ 118904-37-3 ]
[ 71989-35-0 ]
[ 109425-55-0 ]
[ 71989-31-6 ]
[ 84624-17-9 ]
(4S)-MeHex-D-Val-Thr(tBu)-Val-D-Val-D-Pro-Orn(Boc)-D-aIle-D-Dpr-D-aIle-D-Val-OH [ No CAS ]

References: [1]European Journal of Organic Chemistry,2010,p. 2536 - 2543.

11
Fmoc-Leu-preloaded Wang resin, deprotected [ No CAS ]
[ 35661-60-0 ]
[ 35661-60-0 ]
[ 77128-73-5 ]
[ 84624-17-9 ]
[ 1252661-12-3 ]

References: [1]Bioorganic and Medicinal Chemistry,2010,vol. 18,p. 6822 - 6856.

12
C₉H₁₀NO₂Pol [ No CAS ]
[ 122889-11-6 ]
[ 86123-10-6 ]
[ 84624-17-9 ]
[ 135673-97-1 ]
[ 1252661-22-5 ]

References: [1]Bioorganic and Medicinal Chemistry,2010,vol. 18,p. 6822 - 6856.

13
Phe-Wang resin [ No CAS ]
[ 122889-11-6 ]
[ 77128-73-5 ]
[ 84624-17-9 ]
[ 135673-97-1 ]
[ 1190394-43-4 ]

References: [1]Bioorganic and Medicinal Chemistry,2010,vol. 18,p. 6822 - 6856.

14
C₆H₁₂NO₂Pol [ No CAS ]
[ 35661-60-0 ]
[ 103478-62-2 ]
[ 77128-73-5 ]
[ 84624-17-9 ]
[ 1252661-13-4 ]

References: [1]Bioorganic and Medicinal Chemistry,2010,vol. 18,p. 6822 - 6856.

15
C₁₈H₁₇N₂O₃Pol [ No CAS ]
[ 35661-60-0 ]
[ 104091-08-9 ]
[ 84624-17-9 ]
C₂₃H₄₂N₅O₆Pol [ No CAS ]

References: [1]Organic Letters,2010,vol. 12,p. 1652 - 1655.

16
[ 144-49-0 ]
C₁₉H₁₇NO₇S [ No CAS ]
[ 35661-38-2 ]
[ 35661-60-0 ]
[ 104091-08-9 ]
[ 84624-17-9 ]
Fmoc-D-Tyr(O-tBu)-OH [ No CAS ]
N-FMOC-O-tert-butyl-D-threonine [ No CAS ]
(R)-Bgl-D-Tyr-D-Thr-D-Val-D-Glu-D-Leu-D-Ala-NH₂ FA salt [ No CAS ]

References: [1]Journal of Peptide Science,2011,vol. 17,p. 288 - 296.

17
[ 144-49-0 ]
C₁₉H₁₇NO₇S [ No CAS ]
[ 35661-38-2 ]
[ 35661-60-0 ]
[ 104091-08-9 ]
[ 84624-17-9 ]
Fmoc-D-Tyr(O-tBu)-OH [ No CAS ]
N-α-[(9H-fluoren-9-ylmethoxy)carbonyl]-N^G-(2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl)-D-arginine [ No CAS ]
D-Arg-D-Tyr-(R)-Bgl-D-Val-D-Glu-D-Leu-D-Ala-NH₂ FA salt [ No CAS ]

References: [1]Journal of Peptide Science,2011,vol. 17,p. 288 - 296.

18
[ 144-49-0 ]
C₁₉H₁₇NO₇S [ No CAS ]
[ 35661-38-2 ]
[ 35661-60-0 ]
[ 104091-08-9 ]
[ 84624-17-9 ]
N-FMOC-O-tert-butyl-D-threonine [ No CAS ]
N-α-[(9H-fluoren-9-ylmethoxy)carbonyl]-N^G-(2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl)-D-arginine [ No CAS ]
D-Arg-(R)-Bgl-D-Thr-D-Val-D-Glu-D-Leu-D-Ala-NH₂ FA salt [ No CAS ]

References: [1]Journal of Peptide Science,2011,vol. 17,p. 288 - 296.

19
[ 144-49-0 ]
C₁₉H₁₇NO₇S [ No CAS ]
[ 35661-38-2 ]
[ 104091-08-9 ]
[ 84624-17-9 ]
Fmoc-D-Tyr(O-tBu)-OH [ No CAS ]
N-FMOC-O-tert-butyl-D-threonine [ No CAS ]
N-α-[(9H-fluoren-9-ylmethoxy)carbonyl]-N^G-(2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl)-D-arginine [ No CAS ]
D-Arg-D-Tyr-D-Thr-D-Val-D-Glu-(R)-Bgl-D-Ala-NH₂ FA salt [ No CAS ]

References: [1]Journal of Peptide Science,2011,vol. 17,p. 288 - 296.

20
[ 144-49-0 ]
C₁₉H₁₇NO₇S [ No CAS ]
[ 35661-38-2 ]
[ 35661-60-0 ]
[ 104091-08-9 ]
[ 84624-17-9 ]
Fmoc-D-Tyr(O-tBu)-OH [ No CAS ]
N-FMOC-O-tert-butyl-D-threonine [ No CAS ]
(S)-Bgl-D-Tyr-D-Thr-D-Val-D-Glu-D-Leu-D-Ala-NH₂ FA salt [ No CAS ]

References: [1]Journal of Peptide Science,2011,vol. 17,p. 288 - 296.

21
[ 144-49-0 ]
C₁₉H₁₇NO₇S [ No CAS ]
[ 35661-38-2 ]
[ 35661-60-0 ]
[ 104091-08-9 ]
[ 84624-17-9 ]
Fmoc-D-Tyr(O-tBu)-OH [ No CAS ]
N-α-[(9H-fluoren-9-ylmethoxy)carbonyl]-N^G-(2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl)-D-arginine [ No CAS ]
D-Arg-D-Tyr-(S)-Bgl-D-Val-D-Glu-D-Leu-D-Ala-NH₂ FA salt [ No CAS ]

References: [1]Journal of Peptide Science,2011,vol. 17,p. 288 - 296.

22
[ 144-49-0 ]
C₁₉H₁₇NO₇S [ No CAS ]
[ 35661-38-2 ]
[ 35661-60-0 ]
[ 104091-08-9 ]
[ 84624-17-9 ]
N-FMOC-O-tert-butyl-D-threonine [ No CAS ]
N-α-[(9H-fluoren-9-ylmethoxy)carbonyl]-N^G-(2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl)-D-arginine [ No CAS ]
D-Arg-(S)-Bgl-D-Thr-D-Val-D-Glu-D-Leu-D-Ala-NH₂ FA salt [ No CAS ]

References: [1]Journal of Peptide Science,2011,vol. 17,p. 288 - 296.

23
[ 144-49-0 ]
C₁₉H₁₇NO₇S [ No CAS ]
[ 35661-38-2 ]
[ 104091-08-9 ]
[ 84624-17-9 ]
Fmoc-D-Tyr(O-tBu)-OH [ No CAS ]
N-FMOC-O-tert-butyl-D-threonine [ No CAS ]
N-α-[(9H-fluoren-9-ylmethoxy)carbonyl]-N^G-(2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl)-D-arginine [ No CAS ]
D-Arg-D-Tyr-D-Thr-D-Val-D-Glu-(S)-Bgl-D-Ala-NH₂ FA salt [ No CAS ]

References: [1]Journal of Peptide Science,2011,vol. 17,p. 288 - 296.

24
Fmoc-Ala-O-Wang resin [ No CAS ]
[ 124-07-2 ]
[ 29022-11-5 ]
[ 68858-20-8 ]
[ 35661-39-3 ]
[ 35661-40-6 ]
[ 118904-37-3 ]
[ 71989-18-9 ]
[ 73724-45-5 ]
[ 125238-99-5 ]
[ 84624-17-9 ]
N-α-(9-fluorenylmethyloxycarbonyl)-N-γ-tert-butyloxycarbonyl-D-2,4-diaminobutyric acid [ No CAS ]
Protected D-Trp derivative [ No CAS ]
[ 1628113-77-8 ]