331
We present the synthesis of three PDCs with linkers consisting
of different lengths, bonds, and stability (they include various mixtures between ester, amide, carbamate, and oxime bonds), focusing on the description of the synthetic procedures to obtain them.
2 Materials and Equipment
Materials used are commercially available and of the best quality,
unless otherwise stated.
1. D-Lys
6
-GnRH (synthesized via the classical solid-phase peptide synthesis on Rink amide resin, as previously described
[12]) (see Note 1).
2. Gemcitabine base (gemcitabine is Boc-protected on the –NH 2
and the secondary –OH prior to usage, as previously described
[13]) (see Note 1).
3. O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium
hexafluorophosphate (HATU).
4. 1-hydroxybenzotriazole (HOBt).
5. Succinic anhydride.
6. Triisopropylsilane (TIS).
7. N,N-diisopropylethylamine (DIPEA).
8. Trifluoroacetic acid (TFA).
9. Anhydrous N,N-dimethylformamide (DMF).
10. Anhydrous dichloromethane (CH 2 Cl 2 ).
1. D-Lys
6
-GnRH (synthesized via the classical solid-phase peptide synthesis on Rink amide resin, as previously described
[12]).
2. Gemcitabine base (gemcitabine is Boc-protected on the –NH 2
and the secondary –OH prior to usage, as previously described
[13]).
3. Bis(4-nitrophenyl)carbonate.
4. Triisopropylsilane (TIS).
5. N,N-diisopropylethylamine (DIPEA).
6. Trifluoroacetic acid (TFA).
7. Anhydrous N,N-dimethylformamide (DMF).
8. Anhydrous acetonitrile.
1. D-Lys
6
-GnRH (synthesized via the classical step-by-step solidphase peptide synthesis on Rink amide resin, as previously
described [12]) (see Note 1).
2.1 Synthesis
of PDCs
2.1.1 Synthesis of PDCs
Using Succinic Acid
as Linker (Ester
and Amide Bonds)
2.1.2 Synthesis of PDCs
Using Carbamate Bond
in the Linker
2.1.3 Synthesis of PDCs
Using Aminooxy-PEG 4 -
CH 2 CO 2 H as Linker (Amide
and Bond)
Construction of Peptide-Drug Conjugates for Selective Targeting of Malignant Tumor Cells
We present the synthesis of three PDCs with linkers consisting
of different lengths, bonds, and stability (they include various mixtures between ester, amide, carbamate, and oxime bonds), focusing on the description of the synthetic procedures to obtain them.
2 Materials and Equipment
Materials used are commercially available and of the best quality,
unless otherwise stated.
1. D-Lys
6
-GnRH (synthesized via the classical solid-phase peptide synthesis on Rink amide resin, as previously described
[12]) (see Note 1).
2. Gemcitabine base (gemcitabine is Boc-protected on the –NH 2
and the secondary –OH prior to usage, as previously described
[13]) (see Note 1).
3. O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium
hexafluorophosphate (HATU).
4. 1-hydroxybenzotriazole (HOBt).
5. Succinic anhydride.
6. Triisopropylsilane (TIS).
7. N,N-diisopropylethylamine (DIPEA).
8. Trifluoroacetic acid (TFA).
9. Anhydrous N,N-dimethylformamide (DMF).
10. Anhydrous dichloromethane (CH 2 Cl 2 ).
1. D-Lys
6
-GnRH (synthesized via the classical solid-phase peptide synthesis on Rink amide resin, as previously described
[12]).
2. Gemcitabine base (gemcitabine is Boc-protected on the –NH 2
and the secondary –OH prior to usage, as previously described
[13]).
3. Bis(4-nitrophenyl)carbonate.
4. Triisopropylsilane (TIS).
5. N,N-diisopropylethylamine (DIPEA).
6. Trifluoroacetic acid (TFA).
7. Anhydrous N,N-dimethylformamide (DMF).
8. Anhydrous acetonitrile.
1. D-Lys
6
-GnRH (synthesized via the classical step-by-step solidphase peptide synthesis on Rink amide resin, as previously
described [12]) (see Note 1).
2.1 Synthesis
of PDCs
2.1.1 Synthesis of PDCs
Using Succinic Acid
as Linker (Ester
and Amide Bonds)
2.1.2 Synthesis of PDCs
Using Carbamate Bond
in the Linker
2.1.3 Synthesis of PDCs
Using Aminooxy-PEG 4 -
CH 2 CO 2 H as Linker (Amide
and Bond)
Construction of Peptide-Drug Conjugates for Selective Targeting of Malignant Tumor Cells