D
K. Maruyama et al.
Letter
Synlett
References and Notes
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(17) The combined HPLC yield was determined based on the absor-
bances of both folate and the peptide (A254). See Supporting
Information for details.
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(19) The folate-to-protein ratio (N) was determined by using a cali-
bration curve based on the specific absorbances of folate (A347)
and the absorbances of both folate and protein (A278). See the
Supporting Information for details.
(20) Trp-Targeted Conjugation of an ABNO-PEG–Folate to a Pep-
tide; Typical Procedure
Leuprorelin acetate (25.4 g, 0.02 mol, 2.54 L of 10 mg/mL
stock solution), ABNO-PEG4-folate (34.0 g, 0.04 mol, 1.70 L
of 20 mg/mL stock solution), NaNO2 (1.66 g, 0.024 mol, 1.66
L of 1 mg/mL stock solution), and AcOH (0.02 L, 2.00 L of
0.01 L/L stock solution) were dissolved in H2O (12.10 L; final
volume 20 L), and the resulting mixture was stirred at rt for 90
min. The reaction was quenched by the addition of 20 mM
phosphate-buffered saline (PBS; pH 7.4) and the mixture was
analyzed by HPLC and LC/MS. The yield was calculated to be 41%
from the HPLC peak area of the product at 254 nm. HPLC: [YMC-
Triart C18 (4.6 × 150 mm); linear gradient B/A 0–100% (A = 0.1%
aq TFA, B: MeCN) during 2–42 min at a flow rate of 1 mL/min];
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tR = 21.6 min. ESI-MS: m/z calcd [M + 2H]2+ for C97H135N29O22
:
1029.5; found: 1029.6
Trp-Targeted Conjugation of an ABNO-PEG–Folate to a Pro-
tein; Typical Example
Lysozyme (358 g, 0.02 mol, 7.15 L of 50 mg/mL stock solu-
tion), ABNO-PEG4-folate (85.0 g, 0.1 mol, 4.25 L of 20 mg/mL
stock solution), NaNO2 (4.14 g, 0.06 mol, 4.14 L of 1 mg/mL
stock solution), and AcOH (0.1 L, 1.00 L of 1 mg/mL stock
solution) were dissolved in H2O (3.46 L, final volume 20 L),
and the resulting mixture was stirred at rt for 15 min. The
mixture was then transferred into 20 mM PBS (pH 7.4, 200 L)
to quench the reaction. Small molecules were removed by ultra-
filtration (Amicon Ultra, 10 K) (10×; 200 L of PBS was added
each time). The final volume was adjusted to ~ 250 L, and the
UV/Vis spectrum was recorded. The folate-to-protein ratio (N)
was calculated to be 0.72 from the absorbances at 347 and 278
nm, based on the Beer–Lambert law. The solution (80 L) was
exchanged with H2O by ultrafiltration (Amicon Ultra, 10 K), and
the final volume was ~ 40 L. The resulting solution was ana-
lyzed by LC-MS. ESI-Q-TOF MS: m/z [M]+ calcd for
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C
651H1008N206O195S10: 15151.2; found: 15151.6.
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