Cyclic peptides have attracted increasing attention in recent years due to their ability to inhibit protein–protein interactions. Current strategies to prepare cyclic peptides often rely on functional amino acid side chains or the incorporation of unnatural amino acids, thus limiting their structural diversity. Here, we describe the development of a highly versatile peptide macrocyclization strategy through a palladium-catalyzed C(sp3)–H activation and the synthesis of cyclic peptides featuring unique hydrocarbon linkages between the β-carbon of amino acids and the aromatic side chains of Phe and Trp. We demonstrate that such peptides exhibit improved biological properties compared to their acyclic counterparts. Finally, we applied this method in the synthesis of the natural product celogentin C.

Stimuli-responsive hydrogels are “smart” materials with diverse applications. We now report short peptide conjugates with merocyanine (MC) that are able to form stimuli-responsive hydrogels. Systematic investigation reveals that merocyanine is a highly effective promoter for the self-assembly of its oligopeptide conjugates. Hydrogels formed by MC–peptide conjugates showed responses towards light and heat, and their sol–gel phase transition could be manipulated by the reverse photochromism of the corresponding spiropyran moiety. Impressively, a MCI–RGD conjugate formed a supramolecular hydrogel with responses to multiple stimuli, including visible light irradiation, pH change and the presence of Ca2+ ions. An erasable photo-lithograph on the MCI–RGD hydrogel was demonstrated using visible light to write and heat-and-cool treatment to erase for multiple rounds without significant loss of sensitivity.

Cyclic peptides have attracted increasing attention in recent years due to their ability to inhibit protein–protein interactions. Current strategies to prepare cyclic peptides often rely on functional amino acid side chains or the incorporation of unnatural amino acids, thus limiting their structural diversity. Here, we describe the development of a highly versatile peptide macrocyclization strategy through a palladium-catalyzed C(sp3)–H activation and the synthesis of cyclic peptides featuring unique hydrocarbon linkages between the β-carbon of amino acids and the aromatic side chains of Phe and Trp. We demonstrate that such peptides exhibit improved biological properties compared to their acyclic counterparts. Finally, we applied this method in the synthesis of the natural product celogentin C.

Stimuli-responsive hydrogels are “smart” materials with diverse applications. We now report short peptide conjugates with merocyanine (MC) that are able to form stimuli-responsive hydrogels. Systematic investigation reveals that merocyanine is a highly effective promoter for the self-assembly of its oligopeptide conjugates. Hydrogels formed by MC–peptide conjugates showed responses towards light and heat, and their sol–gel phase transition could be manipulated by the reverse photochromism of the corresponding spiropyran moiety. Impressively, a MCI–RGD conjugate formed a supramolecular hydrogel with responses to multiple stimuli, including visible light irradiation, pH change and the presence of Ca2+ ions. An erasable photo-lithograph on the MCI–RGD hydrogel was demonstrated using visible light to write and heat-and-cool treatment to erase for multiple rounds without significant loss of sensitivity.