Effective Penetration of Cell-permeable Peptide Mimic of Tyrosine Residue 654 Domain of β-catenin into Human Renal Tubular Epithelial Cells

Phosphorylation of β-catenin tyrosine residue 654 plays an important role in the epithelial to myofibroblast transition （EMT）. Introducing mimic peptide of tyrosine residue 654 domain of β-catenin into cells may influence phosphorylation of β-catenin tyrosine residue 654. To deliver this mimic peptide into renal epithelial cells, we used penetratin as a vector, which is a novel cell permeable peptide, to deliver hydrophilic molecules into cells. A tyrosine 654 residue domain mimic peptide of β-catenin （PM） with fused penetratin was constructed, purified and then detected for the penetration of the mimic peptide into human renal tubular epithelial cells （HK-2）. The results showed that purified fusion mimic peptide could efficiently and rapidly translocate into human renal tubular epithelial cells. It is concluded that a cell-permeable peptides mimic of tyrosine residue 654 domain of β-catenin was successfully obtained, which may provide a useful reagent for interfering the human renal tubular epithelial-mesenchymal transition.

Nitric oxide-generating compound and bio-clickable peptide mimic for synergistically tailoring surface anti-thrombogenic and anti-microbial dual-functions

Application of extracorporeal circuits and indwelling medical devices has saved many lives.However,it is accompanied with two major complications:thrombosis and infection.To address this issue,we apply therapeutic nitric oxide gas(NO)and antibacterial peptide for synergistically tailoring such devices for surface anti-thrombogenic and antifouling dual functions.Such functional surface is realized by stepwise conjugation of NO-generating compound of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid(DOTA)chelated copper ions(Cu-DOTA)and dibenzylcyclooctyne-(DBCO-)modified antimicrobial peptide based on carbodiimide and click chemistry respectively.The integration of peptide and Cu-DOTA grants the modified surface the ability to not only efficiently inhibit bacterial growth,but also catalytically generate NO from endogenous s-nitrosothiols(RSNO)to reduce adhesion and activation of platelets,preventing the formation of thrombus.We envision that the stepwise synergistic modification strategy by using anticoagulant NO and antibacterial peptide would facilitate the surface multifunctional engineering of extracorporeal circuits and indwelling medical devices,with reduced clinical complications associated with thrombosis and infection.

Alkali-metal hexamethyldisilazide initiated polymerization on alpha-amino acid N-substituted N-carboxyanhydrides for facile polypeptoid synthesis

Polypeptoids have been explored as mimics of polypeptides,owing to polypeptoids'superior stability upon proteolysis.Polypeptoids can be synthesized from one-pot ring-opening polymerization of amino acid N-substituted N-carboxyanhydrides(NNCAs).However,the speed of polymerization of NNCAs can be very slow,especially for NNCAs bearing a bulky N-substitution group.This hindered the exploration on polypeptoids with more diverse structures and functions.Therefore,it is in great need to develop advanced strategies that can accelerate the polymerization on inactive NNCAs.Hereby,we report that lithium/sodium/potassium hexamethyldisilazide(Li/Na/KHMDS)initiates a substantially faster polymerization on NNCAs than do commonly used amine initiators,especially for NNCAs with bulky N-substitution group.This fast NNCA polymerization will increase the structure diversity and application of polypeptoids as synthetic mimics of polypeptides.