For comparison purpose, we also conjugated payload MMAE (auristatin E) and SN38 to hRS7 with DAR value at 8, namely hRS7-VK-MMAE and hRS7-VK-SN38 (Fig. However, our effort to conjugate PTX to hRS7 through a hydrophobic VC linker failed because this molecule precipitated completely from solution during preparation, supporting the concept that combining hydrophobic linkers with ultra-hydrophobic payloads would impair molecular stability of ADC molecules. By using the VK linker, we successfully generated a stable PTX-conjugated ADC and, designated as hRS7-VK-PTX (Fig. 1a) rendered the most stability and hydrophilicity to ADC molecules. In a separate study (unpublished), we have optimized PEGylation in MMAE-conjugated ADCs and found that replacing citrulline with lysine in a cleavable dipeptide “VC linker” and incorporating linear PEG24 to lysine’s free amino group as a parallel branch (peg4-Val-Lys(PEG24)-PAB, designated as “VK linker” in this letter, see (Fig.
0 Comments
Leave a Reply. |