A flexible method for preparation of peptide homo- and heterodimers functionalized with affinity probes, chelating...

Dimerization of peptides can provide high binding entities to serve as targeted diagnostics or therapeutics. We developed methods for the preparation of homo- and heterodimer peptides bearing functional molecules (affinity probes, chelating ligands, or latent conjugating moieties). Monomer peptides, optionally bearing spacer groups, are tethered using a bifunctional linker, (di-succinimidyl glutarate, DSG) to provide the dimers. Protected or unprotected peptides can be employed for dimer assembly. Multiple lysine N(epsilon)-amino groups are controlled using the (4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)-3-methylbutyl (ivDde) protecting group. Functional molecules are optionally incorporated into the component peptides or into the assembled dimer. The methods are efficient and scaleable.