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2 protocols using n n diisopropylethyl amine dipea trifluoroacetic acid tfa

1

Peptide Synthesis with Gadolinium Chelates

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The Fmoc-protected amino acids, 2-chlorotrityl chloride resin, (0-(6-chlorobenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HCTU) and benzotriazol-1-yl-oxy-tris-(pyrrolidino) phosphonium hexafluorophosphate (PyBOP) used for peptide synthesis were purchased from Chem-Impex International, Inc. (Wood Dale, IL, USA). The source of the following chemicals are: Sigma-Aldrich (St. Louis, MO, USA) for anhydrous N,N-diisopropylethyl amine (DIPEA), trifluoroacetic acid (TFA), 2,2′-(ethylenedioxy)diethanethiol (DODT), triisopropylsilane, 4-methyl piperidine, α-cyano-4-hydroxycinnamic acid (CHCA), ammonium bicarbonate, ammonium acetate and meglumine; Fisher Scientific (Pittsburgh, PA, USA) for N,N-dimethylformamide (DMF) and dichloromethane; Apex Bio Technology (Houston, TX, USA) for anhydrous 1-hydroxybenzotriazole (HOBt); Strem Chemicals (Newburyport, MA, USA) for gadolinium (III) acetate tetrahydrate; Macrocyclics, Inc. (Plano, TX, USA) for Fmoc-L-Lys-mono-amide-DOTA-tris (t-Bu ester). Multihance® was purchased from Bracco Diagnostics, Optimark® was purchased from Mallinckrodt Pharmaceuticals (St. Louis, MO, USA), Magnevist® was purchased from Bayer Healthcare Pharmaceuticals, Inc. (Wayne, NJ, USA), and saline was obtained from Hospira, Inc. (Lake Forest, IL, USA).
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2

Peptide Synthesis Protocol Methodology

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All Fmoc amino acids, reagents, and solvents were used without purification. Fmoc amino acids and 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo [4,5-b]pyridinium 3-oxid hexafluorophosphate (HATU) were purchase from AAPPTec, Bachem, Chem-Impex, ChemPep, and PurePep. The Rink amide ChemMatrix resin (catalog number: 7-600-1310) was purchased from Biotage. The 2-chlorotrityl chloride (2-CTC) resin (catalog number: 150301) were purchased from ChemPep. N,N-dimethylformamide (DMF), CH2Cl2, MeCN, MeOH, Et2O, AcOH, Ac2O, N,N-diisopropylethylamine (DIPEA), trifluoroacetic acid (TFA), NH4HCl, NH4HCO3, urea, NaOH, 80% hydrazine hydrate, 2-mercaptoethanol were purchased from Fisher Scientific. Piperidine, triisopropylsilane (TIPS), hydroxybenzotriazole (HOBt), N,N′-diisopropylcarbodiimide (DIC), 2,2′-dithiodipyridine (DTDP), 2,2′-dithiobis (5-nitropyridine) (DTNP), I2, Pd(PPh3)4, 1,3-dimethylbarbituric acid (DMBA), glucose, sodium ascorbate were purchased from Sigma Aldrich. 4-carboxy-3-fluorophenylboronic acid was purchased from Alfa Aesar. Agilent 6120 Quadrupole LC‒MS system was used to acquire the LC chromatograms and mass spectra of samples with Luna® 5 μm C18 100 Å (50 × 2 mm) column (Phenomenex, CA, United States) at 0.4 ml/min with 5% of a H2O/MeCN + 0.1% TFA solution for 1 min followed by a linear gradient from 5% to 95% of a H2O/MeCN + 0.1% TFA solution over 5 min.
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