Bis Thiol & Amine reactive PEGylated Cross-Linker which has been used for enhanced receptor binding, for the design of long-acting conjugates for type 2 diabetes therapeutics and in reorienting the Fab Domains of Trastuzumab Results in Potent HER2 Activators.

This linker can bind two units of thiol carrying molecules, like proteins with solvent accessible cysteins and can in a consecutive step conjugate to amine carrying compounds via standard amid bond formation reaction or in a simple one-step reaction using NHS active ester.

In case the thiol reactive compound shows any receptor interaction the affinity is significantly increased. The amine reactive compound can be an mPEG, simply to increase solubility of the conjugate or other compounds with biological activity. This second conjugation partner can also carrying a PEG spacer with terminal amino group and through this combination a vast variety of PEGylated sophisticated conjugates can very easily be designed. Through this multifunctional property this linker is an ideal key building block for the design of conjugates typically used in combination therapy.

References

• Mono PEGylated Dimeric Exendine-4 as High Receptor Binding and Long-Acting Conjugates for Type 2 Anti-Diabetes Therapeutics. Tae Hyung Kim, Hai Hua Jiang, Seulki Lee, Yu Seock Youn, Chan Woong Park, Youngro Byun, Xiayuan Chen, and Kang Choon Lee; Bioconjugate Chem 2011; 22(4): 625-632. DOI: 10.1021/bc100404x.
• Reorienting the Fab Domains of Trastuzumab Results in Potent HER2 Activators. Justin M. Scheer, Wendy Sandoval, J. Michael Elliott, Lily Shao, Elizabeth Luis, Sock-Cheng Lewin-Koh, Gabriele Schaefer, Richard Vandlen; PLOS ONE 2012; 7(12): e51817. DOI: 10.1371/journal.pone.0051817.