Amino-PEG4-benzyl ester

Cytosolic protein delivery is a prerequisite for protein-based biotechnologies and therapeutics on intracellular targets. Polymers that can complex with proteins to form nano-assemblies represent one of the most important categories of materials, because of the ease of nano-fabrication, high protein loading efficiency, no need for purification, and maintenance of protein bioactivity. Stable protein encapsulation and efficient intracellular liberation are two critical yet opposite processes toward cytosolic delivery, and polymers that can resolve these two conflicting challenges are still lacking. Herein, hyperbranched poly(β-amino ester) (HPAE) with backbone-embedded phenylboronic acid (PBA) is developed to synchronize these two processes, wherein PBA enhanced protein encapsulation via nitrogen-boronate (N-B) coordination while triggered polymer degradation and protein release upon oxidation by H2 O2 in cancer cells. Upon optimization of the branching degree, charge density, and PBA distribution, the best-performing A2-B3-C2-S2 -P2 is identified, which mediates robust delivery of various native proteins/peptides with distinct molecular weights (1.6-430 kDa) and isoelectric points (4.1-10.3) into cancer cells, including enzymes, toxins, antibodies, and CRISPR-Cas9 ribonucleoproteins (RNPs). Moreover, A2-B3-C2-S2 -P2 mediates effective cytosolic delivery of saporin both in vitro and in vivo to provoke remarkable anti-tumor efficacy. Such a potent and universal platform holds transformative potentials for protein pharmaceuticals.

A one-pot three-component protocol has been developed for the synthesis of amino ester-embedded benzimidazoles under metal-free neutral conditions. Sequentially, the methodology involves coupling of an amino ester with 1-fluoro-2-nitrobenzene, reduction of the coupled nitroarene by sodium dithionite, and cyclization of the corresponding diamine with an aldehyde.

Benzyl propionate is an aromatic ester that possesses a fruity odor and is usually found in nature in the composition of some fruits such as plums and melons. This work aimed for the benzyl propionate synthesis by esterification using a new immobilized enzyme preparation with low-cost material from Candida antarctica (NS 88011) and three commercial immobilized lipases (Novozym 435, Lipozyme TL-IM and Lipozyme RM-IM). Novozym 435 had the best performance even when the solvent tert-butanol was absent of the reaction medium. Results from a 22 factorial design showed that an increase in the enzyme amount led to a higher conversion, even when the temperature was kept at the low value. Currently, no research had synthesized successfully benzyl propionate via esterification mediated by lipases; and we reached an ester conversion of ~ 44% after 24 h indicating that it is a promising route for benzyl propionate biotechnological production.