Self-delivery of N-hydroxylethyl peptide assemblies to the cytosol inducing endoplasmic reticulum dilation in cancer cells

Abstract

Inspired by clinical studies on alcohol abuse induced endoplasmic reticulum disruption, we designed a N-hydroxylethyl peptide assembly to regulate the ER stress response in cancer cells.

Enzymatic Noncovalent Synthesis for Targeting Subcellular Organelles

“…Structural exploration of the analogues of 5 suggests that L‐homoarginine at the C‐terminal of the D‐tripeptide likely is responsible for the crescent‐shaped morphology of the assemblies of 6 . Late examples of ER targeting by peptide assemblies [19b,d] are able to selectively induce the death of cancer cells without the need of heterochiral peptides. These results imply that ENS of peptide assemblies provides diverse ways to target ER.…”

Enzyme‐Instructed Self‐Assembly of Peptides: From Concept to Representative Applications

“…As the result of the ALP dephosphorylation, the self‐assembly of 2 is elicited, leading to the formation of the nanofiber assemblies (Figure 2a). In addition to ALP, a variety of enzymes, including carboxylesterase (CES), [33] matrix metalloprotease (MMP), [34] furin, [35] caspase‐3 (CASP3), [36] β‐galactosidase, [37] and β‐lactamase, [38] also has taken part in the enzymatic hydrolysis for EISA of peptides (Figure 2b). The reversed hydrolysis by thermolysin also provides the driving force for EISA [25,39] .…”

Biomaterials based on noncovalent interactions of small molecules

“…Besides ALP, which has a broad spectrum of substrates and fast kinetics, other enzymes, including enterokinase (He et al, 2017[ 35 ]), carboxylesterases (CES) (Zhang et al, 2019[ 112 ]), matrix metalloproteinases (Kalafatovic et al, 2016[ 41 ]), β-galactosidase (Xu et al, 2019[ 97 ]; Akama et al, 2018[ 2 ]), and β-lactamase (Yang et al, 2007[ 105 ]), have acted as the catalysts for EISA. It is also useful to combine enzymatic reaction with fast chemical reactions for EISA.…”

“…Integrating drugs with peptides that are responsive to enzymes upregulated on or inside cancer cells is a useful approach to stabilize some prodrugs until they reach the target sites. Furin-controlled Arg-Val-Arg-Arg-Cys(StBu)-Lys(taxol)-2-cyanobenzothiazole (CBT-Taxol) condensation (Yuan et al, 2015[ 109 ]), ALP-instructed self-assembly of anti-cancer peptide NapG D F D FpYSV (Gao et al, 2019[ 26 ]), and CES-guided release of coumarin (Zhang et al, 2019[ 112 ]) are a few representative examples of this approach.…”