Caspases, a family of cysteine proteases, comprise of highly homologous enzymes that play an important role in apoptotic cell death. Caspase-3 shows key functions in apoptosis, mediating apoptotic cascade from the int...Caspases, a family of cysteine proteases, comprise of highly homologous enzymes that play an important role in apoptotic cell death. Caspase-3 shows key functions in apoptosis, mediating apoptotic cascade from the intrinsic and extrinsic activation pathways. Therefore, caspase-3 is an attractive target for therapeutic intervention. For instance, inhibitors of caspase-3 have been described as promising cardioprotectants, neuroprotectants and antiarthritic agents. A novel peptidomimetic inhibitor of caspase-3, has been designed, which still has the properties of a reversible inhibitor, while the P1 site at the C-terminal remains, and only L-amino acid has been replaced by D-amino acid. Also presented here is the synthesis of the inhibitor and its inhibitory activity against caspase-3, which was tested by the fluorescent activity assay.展开更多
Engineered scaffolds for bone tissue regeneration are designed to promote cell adhesion,growth,proliferation and differentiation.Recently,covalent and selective functionalization of glass and titanium surfaces with an...Engineered scaffolds for bone tissue regeneration are designed to promote cell adhesion,growth,proliferation and differentiation.Recently,covalent and selective functionalization of glass and titanium surfaces with an adhesive peptide(HVP)mapped on[351e359]sequence of human Vitronectin allowed to selectively increase osteoblast attachment and adhesion strength in in vitro assays,and to promote osseointegration in in vivo studies.For the first time to our knowledge,in this study we investigated the resistance of adhesion sequences to proteolytic digestion:HVP was completely cleaved after 5 h.In order to overcome the enzymatic degradation of the native peptide under physiological conditions we synthetized three analogues of HVP sequence.A retro-inverted peptide D-2HVP,composed of D amino acids,was completely stable in serum-containing medium.In addition,glass surfaces functionalized with D-2HVP increased human osteoblast adhesion as compared to the native peptide and maintained deposition of calcium.Interestingly,D-2HVP increased expression of IBSP,VTN and SPP1 genes as compared to HVP functionalized surfaces.Total internal reflection fluorescence microscope analysis showed cells with numerous filopodia spread on D-2HVP-functionalized surfaces.Therefore,the D-2HVP sequence is proposed as new osteoblast adhesive peptide with increased bioactivity and high proteolytic resistance.展开更多
文摘Caspases, a family of cysteine proteases, comprise of highly homologous enzymes that play an important role in apoptotic cell death. Caspase-3 shows key functions in apoptosis, mediating apoptotic cascade from the intrinsic and extrinsic activation pathways. Therefore, caspase-3 is an attractive target for therapeutic intervention. For instance, inhibitors of caspase-3 have been described as promising cardioprotectants, neuroprotectants and antiarthritic agents. A novel peptidomimetic inhibitor of caspase-3, has been designed, which still has the properties of a reversible inhibitor, while the P1 site at the C-terminal remains, and only L-amino acid has been replaced by D-amino acid. Also presented here is the synthesis of the inhibitor and its inhibitory activity against caspase-3, which was tested by the fluorescent activity assay.
文摘Engineered scaffolds for bone tissue regeneration are designed to promote cell adhesion,growth,proliferation and differentiation.Recently,covalent and selective functionalization of glass and titanium surfaces with an adhesive peptide(HVP)mapped on[351e359]sequence of human Vitronectin allowed to selectively increase osteoblast attachment and adhesion strength in in vitro assays,and to promote osseointegration in in vivo studies.For the first time to our knowledge,in this study we investigated the resistance of adhesion sequences to proteolytic digestion:HVP was completely cleaved after 5 h.In order to overcome the enzymatic degradation of the native peptide under physiological conditions we synthetized three analogues of HVP sequence.A retro-inverted peptide D-2HVP,composed of D amino acids,was completely stable in serum-containing medium.In addition,glass surfaces functionalized with D-2HVP increased human osteoblast adhesion as compared to the native peptide and maintained deposition of calcium.Interestingly,D-2HVP increased expression of IBSP,VTN and SPP1 genes as compared to HVP functionalized surfaces.Total internal reflection fluorescence microscope analysis showed cells with numerous filopodia spread on D-2HVP-functionalized surfaces.Therefore,the D-2HVP sequence is proposed as new osteoblast adhesive peptide with increased bioactivity and high proteolytic resistance.
