576-19-2

Basic information

• Product Name: Biocytin
• Synonyms: NE-BIOTYNYL-L-LYSINE;N-EPSILON-BIOTIN-L-LYSINE;N-EPSILON-(+)-BIOTINYL-L-LYSINE;N-EPSILON-BIOTINYL-L-LYSINE;N-EPSILON-D-BIOTINYL-L-LYSINE;LYSINE(BIOTINYL)-OH;L-BIOCYTIN;EPSILON-BIOTINOYL-L-LYSINE
• CAS NO: 576-19-2
• Molecular Formula: C₁₆H₂₈N₄O₄S
• Molecular Weight: 372.48
• Product Categories: Biotin Derivatives;Amino Acids & Derivatives
• Mol File: 576-19-2.mol
• Article Data: 6

Chemical Properties

• Melting Point: ~245 °C (dec.)
• Boiling Point: 748 °C at 760 mmHg
• Flash Point: 406.2 °C
• Appearance: White Solid
• Density: 1.234
• Vapor Pressure: 1.75E-24mmHg at 25°C
• Refractive Index: 1.547
• Storage Temp.: −20°C
• Solubility: Aqueous Base (Slightly), Water (Slightly, Sonicated)
• PKA: 2.53±0.24(Predicted)
• Merck: 13,1227
• BRN: 97197
• CAS DataBase Reference: Biocytin(CAS DataBase Reference)
• NIST Chemistry Reference: Biocytin(576-19-2)
• EPA Substance Registry System: Biocytin(576-19-2)

Safety Data

• WGK Germany: 3
• Hazardous Substances Data: 576-19-2(Hazardous Substances Data)

Usage

Description

Biocytin is a conjugate of biotin and lysine known formally as ε-N-(d-biotinyl)-L-lysine. The addition of lysine to biotin increases the chain length extending from biotin, allowing the synthesis of medium-chain reagents. It also provides terminal carboxyl and amino groups for derivatization or conjugation to proteins and other molecules. Covalent linking reactions typically involve carbodiimide or NHS-ester crosslinking chemistries. Biocytin is also used as an anterograde, retrograde, or intracellular neuroanatomical tracer that is fixable with aldehyde-based fixatives. For this and other applications, biocytin is detected with avidin or streptavidin probes.

Chemical Properties

White Solid

Uses

Different sources of media describe the Uses of 576-19-2 differently. You can refer to the following data:
1. Useful for the synthesis of Biocytin containing peptides to study the mechanism of reactions catalyzed by biotin - containing enzymes
2. Biocytin can be used as a versatile fluorescent marker for neuroanatomical investigations and for a biotinidase assay.
3. Biocytin is used as a substrate to study the specificity and kinetics of biotinidase(s), to measure biotinidase deficiency and as a model compound to study various uptake mechanisms of cells and tissues. Biocytin has been used to label neurons, medium spiny neurons and optic nerves.

Definition

ChEBI: A monocarboxylic acid amide that results from the formal condensation of the carboxylic acid group of biotin with the N6-amino group of L-lysine.

Biological Activity

Versatile marker used in anterograde, retrograde and intracellular neuroanatomical investigations and in biotinidase assays. Displays high solubility in aqueous solutions and has a low molecular weight facilitating injection using micropipettes. Can be incorporated with a variety of avidin and streptavidin conjugates for detection by light, fluorescence or electron microscope.

Biochem/physiol Actions

Biocytin is an adduct of lysine and biotin. It is hydrolyzed by biotinidase, which acts on peptide-incorporated biotin or free biotin. Biocytin acts as a coenzyme.

Purification Methods

Recrystallise biocytin rapidly from dilute MeOH or Me2CO. It can also be recrystallised from H2O by slow evaporation or by dissolving in the minimum volume of H2O and adding Me2CO until solid separates. It is freely soluble in H2O and AcOH but insoluble in Me2CO. [Wolf et al. J Am Chem Soc 74 2002 1952, 72 1048 1950.] It has been purified by chromatography on superfiltrol-Celite, Al2O3 and by countercurrent distribution and then recrystallised [IR: Peck et al. J Am Chem Soc 74 1991 1952]. The hydrochloride recrystallises from aqueous Me2CO/HCl and has m 227o (dec). [Beilstein 27 III/IV 7984.]

InChI:InChI=1/C16H28N4O4S/c17-10(15(22)23)5-3-4-8-18-13(21)7-2-1-6-12-14-11(9-25-12)19-16(24)20-14/h10-12,14H,1-9,17H2,(H,18,21)(H,22,23)(H2,19,20,24)

Synthetic route

N-(4-((S)-5'-oxo-9λ4-boraspiro[bicyclo[3.3.1]nonane-9,2'-[1,3,2]oxazaborolidin]-4'-yl)butyl)-5-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamide → biocytin (576-19-2)

Conditions	Yield
With tetrabutyl ammonium fluoride In tetrahydrofuran; water at 20℃; for 2h;	73%

L-lysine (56-87-1) + biotin chloride (91853-90-6) → biocytin (576-19-2)

Conditions	Yield
With sodium hydroxide; chloroform

N2-formyl-N6-[5-((3aS)-2-oxo-(3ar,6ac)-hexahydro-thieno[3,4-d]imidazol-4t-yl)-valeryl]-L-lysine (857358-40-8) → biocytin (576-19-2)

Conditions	Yield
With hydrogenchloride

biotin methyl ester (608-16-2) → biocytin (576-19-2)

Conditions	Yield
With toluene; 1,2,4-Trichlorobenzene

Boc-Lys(biotinyl)-OH (62062-43-5) → biocytin (576-19-2)

Conditions	Yield
With methoxybenzene; trifluoroacetic acid

L-lysine (56-87-1) + biotin-ethyl ester → biocytin (576-19-2)

Conditions	Yield
With toluene; 1,2,4-Trichlorobenzene

biotin N-Hydroxysuccinimide ester (35013-72-0) → biocytin (576-19-2)

Conditions	Yield
Stage #1: biotin N-Hydroxysuccinimide ester With sodium hydrogencarbonate In water; N,N-dimethyl-formamide Stage #2: With ethylenediaminetetraacetic acid In water
Multi-step reaction with 2 steps 1: sodium hydroxide / 1,4-dioxane; water / 20 °C / pH 8 - 8.5 2: 1,8-diazabicyclo[5.4.0]undec-7-ene / N,N-dimethyl-formamide / 1 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1: sodium hydroxide / 1,4-dioxane / 22 - 25 °C / pH 8 - 8.5 2: 1,8-diazabicyclo[5.4.0]undec-7-ene / N,N-dimethyl-formamide / 1 h / 22 - 25 °C View Scheme

Nα-formyl-L-lysine (19729-28-3) → biocytin (576-19-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: pyridine 2: aqueous HCl View Scheme

biotin chloride (91853-90-6) → biocytin (576-19-2)

Conditions	Yield
Multi-step reaction with 2 steps 2: toluene; 1,2,4-trichloro-benzene View Scheme
Multi-step reaction with 2 steps 1: pyridine 2: aqueous HCl View Scheme

N6-[(benzyloxy)carbonyl]-L-lysine (1155-64-2) → biocytin (576-19-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: acetic acid anhydride / und Hydrieren des Reaktionsprodukts an Palladium 2: pyridine 3: aqueous HCl View Scheme

Boc-Lys-OH (13734-28-6) → biocytin (576-19-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: Py, aq. NaOH 2: aq. CF3CO2H, anisole View Scheme

D-(+)-biotin 2-nitrophenyl ester (33755-53-2) → biocytin (576-19-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: Py, aq. NaOH 2: aq. CF3CO2H, anisole View Scheme

5-((3aS)-2-oxo-1-trifluoroacetyl-(3ar,6ac)-hexahydro-thieno[3,4-d]imidazol-4t-yl)-pentanoic acid 4-nitro-phenyl ester (62062-42-4) → biocytin (576-19-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: aq. EtOH / Heating 2: Py, aq. NaOH 3: aq. CF3CO2H, anisole View Scheme

biotin (58-85-5) → biocytin (576-19-2)

Conditions	Yield
Multi-step reaction with 4 steps 1: 4-nitro-phenol, Py / 50 °C 2: aq. EtOH / Heating 3: Py, aq. NaOH 4: aq. CF3CO2H, anisole View Scheme
Multi-step reaction with 3 steps 1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 20 °C 2: sodium hydroxide / 1,4-dioxane; water / 20 °C / pH 8 - 8.5 3: 1,8-diazabicyclo[5.4.0]undec-7-ene / N,N-dimethyl-formamide / 1 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 22 - 25 °C 2: sodium hydroxide / 1,4-dioxane / 22 - 25 °C / pH 8 - 8.5 3: 1,8-diazabicyclo[5.4.0]undec-7-ene / N,N-dimethyl-formamide / 1 h / 22 - 25 °C View Scheme

N-α-Fmoc-N-ε-biotinyl-L-lysine (146987-10-2) → biocytin (576-19-2)

Conditions	Yield
With 1,8-diazabicyclo[5.4.0]undec-7-ene In N,N-dimethyl-formamide at 20℃; for 1h;
With 1,8-diazabicyclo[5.4.0]undec-7-ene In N,N-dimethyl-formamide at 22 - 25℃; for 1h;

L-lysine (56-87-1) + biotin (58-85-5) → biocytin (576-19-2)

Conditions	Yield
With 1-hydroxy-pyrrolidine-2,5-dione; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; sodium hydroxide In dichloromethane at 45℃; for 2h; pH=7.4;

[CpFe(CO)2(η1-N-3-isothiocyanatophtalimidato)] (192222-85-8) + biocytin (576-19-2) → [CpFe(CO)2(NC8H3O2NHC(S)NHCH(COOH)(CH2)4NHCO(CH2)4C5H7N2OS)]

Conditions	Yield
With triethylamine In water; N,N-dimethyl-formamide (Ar); stirring of soln. of CpFe(CO)2(NC8H3O2NCS), biocytin and Et3N in water at room temp. for 2 h; evapn. to dryness, dissolving in water, acidification to pH 3 with 0.6 MHCl, pptn., elem. anal.;	94%

2-(methylsulfonyl)ethyl succinimidyl carbonate (57903-15-8) + biocytin (576-19-2) → (S)-2-(2-Methanesulfonyl-ethoxycarbonylamino)-6-[5-((3aR,6S,6aS)-2-oxo-hexahydro-thieno[3,4-d]imidazol-6-yl)-pentanoylamino]-hexanoic acid

Conditions	Yield
With triethylamine In water; acetonitrile for 16h; Ambient temperature;	93%

[CpFe(CO)2(η1-N-4-isothiocyanatophtalimidato)] (192222-87-0) + water (7732-18-5) + biocytin (576-19-2) → [CpFe(CO)2(NC8H3O2NHC(S)NHCH(COOH)(CH2)4NHCO(CH2)4C5H7N2OS)] monohydrate

Conditions	Yield
With triethylamine In water; N,N-dimethyl-formamide (Ar); stirring of soln. of CpFe(CO)2(NC8H3O2NCS), biocytin and Et3N in water at room temp. for 2 h; evapn. to dryness, dissolving in water, acidification to pH 3 with 0.6 MHCl, pptn., elem. anal.;	93%

1-<<4-<3-(trifluoromethyl)-3H-diazirin-3-yl>benzoyl>oxy>-2,5-pyrrolidinedione (87736-89-8) + biocytin (576-19-2) → Nα-(4-(1-azi-2,2,2-trifluoroethyl)benzoyl)-L-biocytin

Conditions	Yield
With sodium hydroxide In N,N-dimethyl-formamide Ambient temperature;	91%

p-benzoylbenzoic acid N-hydroxysuccinimide ester (91990-88-4) + biocytin (576-19-2) → Nα-(4-benzoylbenzoyl)-L-biocytin (165898-24-8)

Conditions	Yield
With sodium hydroxide In water; N,N-dimethyl-formamide	90%
With sodium hydroxide In N,N-dimethyl-formamide Ambient temperature;	82%

succinimidyl 4-azido-2,3,5,6-tetrafluorobenzoate (126695-58-7) + biocytin (576-19-2) → 2-(4-azido-2,3,5,6-tetrafluorobenzamido)-6-[5-(hexahydro-2-oxo-1H-thieno[3,4-d]imidazol-6-yl)pentanamido]hexanoic acid (165898-22-6)

Conditions	Yield
With sodium hydroxide In N,N-dimethyl-formamide at 20℃;	89%
With sodium hydroxide In N,N-dimethyl-formamide Ambient temperature;	85%

1-<<<2-nitro-4-<3-(trifluoromethyl)-3H-diazirin-3-yl>phenoxy>acetyl>oxy>-2,5-pyrrolidinedione (125680-85-5) + biocytin (576-19-2) → (S)-2-{2-[2-Nitro-4-(3-trifluoromethyl-3H-diazirin-3-yl)-phenoxy]-acetylamino}-6-[5-((3aR,6S,6aS)-2-oxo-hexahydro-thieno[3,4-d]imidazol-6-yl)-pentanoylamino]-hexanoic acid (178484-35-0)

Conditions	Yield
With sodium hydrogencarbonate In water; N,N-dimethyl-formamide; acetonitrile for 1h; Ambient temperature;	89%

[CpFe(CO)2(η1-N-4-isothiocyanatobenzenesulfonamido)] (546094-91-1) + water (7732-18-5) + biocytin (576-19-2) → [CpFe(CO)2(NHSO2C6H4NHC(S)NHCH(COOH)(CH2)4NHCO(CH2)4C5H7N2OS)] thihydrate

Conditions	Yield
With triethylamine In water; N,N-dimethyl-formamide (Ar); stirring of soln. of CpFe(CO)2(NHSO2C6H4NCS), biocytin and Et3N inwater at room temp. for 2 h; evapn. to dryness, dissolving in water, acidification to pH 3 with 0.6 MHCl, pptn., elem. anal.;	62%

9-methoxy-9-BBN (38050-71-4) + biocytin (576-19-2) → N-(4-((S)-5'-oxo-9λ4-boraspiro[bicyclo[3.3.1]nonane-9,2'-[1,3,2]oxazaborolidin]-4'-yl)butyl)-5-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamide

Conditions	Yield
In methanol; hexane for 4h; Reflux;	58%

4-azidobenzoic acid N-hydroxysuccinimide ester (53053-08-0) + biocytin (576-19-2) → C23H31N7O5S

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 22 - 25℃;	30.4%
With N-ethyl-N,N-diisopropylamine at 20℃;

nitroveratryloxycarbonyl chloride (42855-00-5) + biocytin (576-19-2) → (S)-2-(4,5-Dimethoxy-2-nitro-benzyloxycarbonylamino)-6-[5-((3aR,6S,6aS)-2-oxo-hexahydro-thieno[3,4-d]imidazol-6-yl)-pentanoylamino]-hexanoic acid

Conditions	Yield
With sodium carbonate In tetrahydrofuran; water for 3h;

biocytin (576-19-2) → (S)-2-(4-Azido-2,3,5,6-tetrafluoro-benzoylamino)-6-[5-((3aR,6S,6aS)-2-oxo-hexahydro-thieno[3,4-d]imidazol-6-yl)-pentanoylamino]-hexanoic acid 2,5-dioxo-pyrrolidin-1-yl ester (249749-25-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: 89 percent / aq. NaOH / dimethylformamide / 20 °C 2: 77 percent / dicyclohexylcarbodiimide / dimethylformamide / 12 h / 20 °C View Scheme

biocytin (576-19-2) → 4-Azido-N-{(S)-1-(2-{2-[4-(4-chloro-2-fluoro-phenylamino)-6-methoxy-quinazolin-7-yloxy]-ethoxy}-ethylcarbamoyl)-5-[5-((3aR,6S,6aS)-2-oxo-hexahydro-thieno[3,4-d]imidazol-6-yl)-pentanoylamino]-pentyl}-2,3,5,6-tetrafluoro-benzamide

Conditions	Yield
Multi-step reaction with 3 steps 1: 89 percent / aq. NaOH / dimethylformamide / 20 °C 2: 77 percent / dicyclohexylcarbodiimide / dimethylformamide / 12 h / 20 °C 3: 98 percent / dimethylformamide / 12 h / 20 °C View Scheme

biocytin (576-19-2) → (S)-2-(4,5-Dimethoxy-2-nitro-benzyloxycarbonylamino)-6-[5-((3aR,6aS)-2-oxo-hexahydro-thieno[3,4-d]imidazol-6-yl)-pentanoylamino]-hexanoic acid cyanomethyl ester

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium carbonate / H2O; tetrahydrofuran / 3 h 2: triethylamine / dimethylformamide View Scheme

biocytin (576-19-2) → 1-(N-(Nα-(4-benzoylbenzoyl)-L-biocytinoyl)amino)-6-(N'-pepstatinoylamino)hexane

Conditions	Yield
Multi-step reaction with 4 steps 1: 82 percent / aq. NaOH / dimethylformamide / Ambient temperature 2: 86 percent / diisopropylethylamine, HOAT, EDAC / dimethylformamide / Ambient temperature 3: HCl / dioxane / 1 h / Ambient temperature 4: diisopropylethylamine, HOAT, EDAC / dimethylformamide / Ambient temperature View Scheme

biocytin (576-19-2) → N-{(S)-1-(6-Amino-hexylcarbamoyl)-5-[5-((3aR,6S,6aS)-2-oxo-hexahydro-thieno[3,4-d]imidazol-6-yl)-pentanoylamino]-pentyl}-4-benzoyl-benzamide

Conditions	Yield
Multi-step reaction with 3 steps 1: 82 percent / aq. NaOH / dimethylformamide / Ambient temperature 2: 86 percent / diisopropylethylamine, HOAT, EDAC / dimethylformamide / Ambient temperature 3: HCl / dioxane / 1 h / Ambient temperature View Scheme

biocytin (576-19-2) → 1-(N-(Nα-(4-benzoylbenzoyl)-L-biocytinoyl)amino)-6-(N'-boc-amino)hexane (165898-25-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 82 percent / aq. NaOH / dimethylformamide / Ambient temperature 2: 86 percent / diisopropylethylamine, HOAT, EDAC / dimethylformamide / Ambient temperature View Scheme

biocytin (576-19-2) → {(S)-1-(2-Amino-ethylcarbamoyl)-5-[5-((3aR,6S,6aS)-2-oxo-hexahydro-thieno[3,4-d]imidazol-6-yl)-pentanoylamino]-pentyl}-carbamic acid 2-methanesulfonyl-ethyl ester (168639-65-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: 93 percent / Et3N / H2O; acetonitrile / 16 h / Ambient temperature 2: 70 percent / Et3N, HOBt, CMC metho-p-toluene sulfonate / H2O; acetonitrile / 16 h / Ambient temperature 3: aq. TFA / Ambient temperature View Scheme

biocytin (576-19-2) → {(S)-1-(2-tert-Butoxycarbonylamino-ethylcarbamoyl)-5-[5-((3aR,6S,6aS)-2-oxo-hexahydro-thieno[3,4-d]imidazol-6-yl)-pentanoylamino]-pentyl}-carbamic acid 2-methanesulfonyl-ethyl ester (168639-75-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 93 percent / Et3N / H2O; acetonitrile / 16 h / Ambient temperature 2: 70 percent / Et3N, HOBt, CMC metho-p-toluene sulfonate / H2O; acetonitrile / 16 h / Ambient temperature View Scheme

biocytin (576-19-2) → {(S)-1-{2-[3-(4-Hydroxy-phenyl)-propionylamino]-ethylcarbamoyl}-5-[5-((3aR,6S,6aS)-2-oxo-hexahydro-thieno[3,4-d]imidazol-6-yl)-pentanoylamino]-pentyl}-carbamic acid 2-methanesulfonyl-ethyl ester

Conditions	Yield
Multi-step reaction with 4 steps 1: 93 percent / Et3N / H2O; acetonitrile / 16 h / Ambient temperature 2: 70 percent / Et3N, HOBt, CMC metho-p-toluene sulfonate / H2O; acetonitrile / 16 h / Ambient temperature 3: aq. TFA / Ambient temperature 4: 73 percent / DIPEA / acetonitrile; H2O / 20 h / Ambient temperature View Scheme

Upstream product

• 56-87-1 L-lysine 
• 1155-64-2 N₆-[(benzyloxy)carbonyl]-L-lysine 
• 13734-28-6 Boc-Lys-OH 
• 146987-10-2 N-α-Fmoc-N-ε-biotinyl-L-lysine 
• 58-85-5 biotin 
• 62062-42-4 5-((3aS)-2-oxo-1-trifluoroacetyl-(3ar,6ac)-hexahydro-thieno[3,4-d]imidazol-4t-yl)-pentanoic acid 4-nitro-phenyl ester 
• 33755-53-2 D-(+)-biotin 2-nitrophenyl ester 
• 19729-28-3 N^α-formyl-L-lysine 
• 35013-72-0 biotin N-Hydroxysuccinimide ester 
• 62062-43-5 Boc-Lys(biotinyl)-OH 
• 608-16-2 biotin methyl ester 
• 91853-90-6 biotin chloride 
• 857358-40-8 N²-formyl-N⁶-[5-((3aS)-2-oxo-(3ar,6ac)-hexahydro-thieno[3,4-d]imidazol-4t-yl)-valeryl]-L-lysine 

Downstream Products

• 249749-25-5 (S)-2-(4-Azido-2,3,5,6-tetrafluoro-benzoylamino)-6-[5-((3aR,6S,6aS)-2-oxo-hexahydro-thieno[3,4-d]imidazol-6-yl)-pentanoylamino]-hexanoic acid 2,5-dioxo-pyrrolidin-1-yl ester 
• 58-85-5 biotin 
• 178484-35-0 (S)-2-{2-[2-Nitro-4-(3-trifluoromethyl-3H-diazirin-3-yl)-phenoxy]-acetylamino}-6-[5-((3aR,6S,6aS)-2-oxo-hexahydro-thieno[3,4-d]imidazol-6-yl)-pentanoylamino]-hexanoic acid 
• 165898-24-8 N^α-(4-benzoylbenzoyl)-L-biocytin 
• 165898-22-6 2-(4-azido-2,3,5,6-tetrafluorobenzamido)-6-[5-(hexahydro-2-oxo-1H-thieno[3,4-d]imidazol-6-yl)pentanamido]hexanoic acid 
• 165898-25-9 1-(N-(N^α-(4-benzoylbenzoyl)-L-biocytinoyl)amino)-6-(N'-boc-amino)hexane 

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