A flexible method for preparation of peptide homo‐ and heterodimers functionalized with affinity probes, chelating ligands, and latent conjugating groups

Abstract

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.