Peptide ligation is an indispensable step in the chemical synthesis of target peptides and proteins that are difficult to synthesize at once by a solid-phase synthesis. The ligation reaction is generally conducted with two peptide fragments at a high aqueous concentration to increase the reaction rate; however, this often causes unpredictable aggregation and precipitation of starting or resulting peptides due to their hydrophobicities. Here, we have developed a novel peptide ligation strategy harnessing the two intrinsic characteristics of oligodeoxynucleotides (ODNs), i.e., their hydrophilicity and hybridization ability, which allowed increases in the water solubility of peptides and the reaction kinetics due to the proximity effect, respectively. Peptide−ODN conjugates that can be cleaved to regenerate native peptide sequences were synthesized using novel lysine derivatives containing conjugation handles and photolabile linkers, via solid-phase peptide synthesis and subsequent conjugation to 15-mer ODNs. Two complementary conjugates were applied to carbodiimide-mediated peptide ligation on a DNA scaffold, and the subsequent DNA removal was conducted by photoirradiation in a traceless fashion. This DNA scaffold-assisted ligation resulted in a significant acceleration of the reaction kinetics and enabled ligation of a hydrophobic peptide at a micromolar concentration. On the basis of this chemistry, a simultaneous ligation of three different peptide fragments on two different DNA scaffolds has been conducted for the first time.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.