The non-degradability of vinyl polymers has long limited their use in biomedical applications. In this article, the authors demonstrate a system based on acrylamide and cyclic ketene acetals to obtain...

Fully recombinant protein-based biomaterials execute complex Boolean logic for user-programmable material degradation and concomitant therapeutic cargo release. Biologics, such as growth factors, can...

Fully recombinant protein-based biomaterials execute complex Boolean logic for user-programmable material degradation and concomitant therapeutic cargo release. Biologics, such as growth factors, can...

arXiv abstract link

A detached body part is supposed to decay and eventually die. However, scientists have now discovered a remarkable exception on the floor of the North Atlantic and Arctic oceans. Detached body parts from a sea cucumber called Psolus fabricii not only survived after being separated from the animal but also healed themselves, absorbed nutrients, and continued living for more than three years. “These findings challenge our basic understanding of tissue resilience and degradability,” the researchers note in their study. Biologists have known that some animals can regrow lost body parts. Salamanders can famously regenerate limbs, sea stars can regrow arms, and, while we’re at it, many sea cucumbers can rebuild damaged organs. However, the detached body parts themselves were generally assumed to wither and die. This newly discovered tissue appears to follow a different set of rules. An accidental discovery The discovery began unexpectedly in a laboratory at Memorial University in Canada. Researchers were keeping live Psolus fabricii sea cucumbers in aquariums when they noticed that some tube feet (the small appendages the animals use to grip surfaces) had been left behind on the tank walls after the animals were removed. At first, the observation did not seem unusual. Sea...

We developed a novel domino polymerization to synthesize reductively degradable poly(disulfide)s with tunable side chains. A novel monomer bearing thiolactone and pyridyl disulfide groups reacts with various amines, enabling continuous ring-opening and disulfide exchange. The resulting polymers show reductive degradability, pH-responsive solubility, and can form degradable gels, offering versatile applications. ABSTRACT The environmental persistence of conventional plastics has driven the development of degradable polymers with functional versatility. Poly(disulfide)s are particularly attractive due to their reductive degradability and environmentally triggered disassembly. In this study, we report a domino polymerization strategy that enables the rapid and modular synthesis of functional poly(disulfide)s with degradable main chains and diverse side-chain structures. This method utilizes a single monomer, N-(2-oxotetrahydrothiophen-3-yl)-3-(pyridin-2-yldisulfanyl)propanamide (PDTL), which contains both thiolactone (TL) and pyridyl disulfide (PDS) moieties. Polymerization is initiated by TL ring-opening with commercially available amines, generating thiol groups that undergo disulfide exchange with PDS moieties of other monomers, resulting in chain propagation. The method accommodates primary, secondary amines, and ammonia, allowing incorporation of alkyl, allyl, propargyl, hydroxyl, carboxyl, amide, and tertiary amine functionalities. The reductive degradability of the poly(disulfide)s is confirmed using gel permeation chromatography and mass spectrometry. Furthermore, it is found that pH-responsive properties appear in poly(disulfide)s possessing dimethylamino groups, where water solubility can be regulated in response to pH. Domino polymerization is further applied to synthesize reductively degradable poly(disulfide) gels using multi-functional amines. This polymerization technique will lead to the development of reductively degradable polymers with various functions for use in various applications in the future.

Tong et al. describe a chemical genetic system to evaluate the degradability of deubiquitylase (DUBs) enzymes by PROTACs that do not inhibit their catalytic activity. They find that some Dubs are readily degradable, others resist degradation through auto-deubiquitylation, and some are inherently poor proteasome substrates because they are difficult to unfold.

Tong et al. describe a chemical genetic system to evaluate the degradability of deubiquitylase (DUBs) enzymes by PROTACs that do not inhibit their catalytic activity. They find that some Dubs are readily degradable, others resist degradation through auto-deubiquitylation, and some are inherently poor proteasome substrates because they are difficult to unfold.

Targeted protein degradation selectively eliminates disease-causing proteins by using small-molecule degraders. Here, we integrate fundamental biology with small molecules to study a methylation-driven signal for lysosomes. Insight into methylarginine degrons enables the development of methylarginine-targeting chimeras (MrTACs), which degrade pathogenic proteins by recruiting protein arginine methyltransferases (PRMTs). We assess the utility of existing PRMT inhibitors for MrTAC design and demonstrate that group-transfer chemistry can transform inhibitory ligands into silent recruiters, thereby generating the first series of fully endogenous MrTACs.