RESUMO
Herein, we report the facile preparation of cell-targeted platinum nanoparticles (PtNPs), through the design of peptides that, as a single molecule added in small concentration during the synthesis, control the size of PtNP clusters during their growth, stabilise the PtNPs in aqueous suspension and enable the functionalisation of the PtNPs with a versatile range of cell-targeting ligands. Water-soluble PtNPs targeted respectively at blood group antigens and at integrin receptors are demonstrated.
Assuntos
Bioquímica/métodos , Nanopartículas Metálicas/química , Platina/química , Células 3T3/efeitos dos fármacos , Animais , Antígenos de Grupos Sanguíneos/metabolismo , Concanavalina A/química , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Humanos , Integrina alfaVbeta3/metabolismo , Ligantes , Nanopartículas Metálicas/ultraestrutura , Camundongos , Microscopia Eletrônica de Transmissão , Peptídeos/síntese química , Peptídeos/química , Platina/farmacologia , Ratos , SolubilidadeRESUMO
The α4ß7 integrin is a well-known target for the development of drugs against various inflammatory disease states including inflammatory bowel disease, type 1 diabetes and multiple sclerosis. The synthesis of a small library of cell-permeable ß7 integrin inhibitors based on the peptide biotin-R(8)ERY is reported, in which the tyrosine residue has been modified by using the Suzuki-Miyaura cross-coupling reaction. The synthesised peptidomimetics were evaluated in a cell adhesion assay and shown to inhibit Mn(2+)-activated adhesion of mouse TK-1 T cells to mouse MAdCAM-1. All of the synthesised peptidomimetics are more active than our previously reported lead compound biotin-R(8)ERY with two of the analogues, 6 and 7, exhibiting IC(50) values of <15 µM.
Assuntos
Biotina/análogos & derivados , Moléculas de Adesão Celular/antagonistas & inibidores , Integrinas/antagonistas & inibidores , Oligopeptídeos/farmacologia , Peptidomiméticos/farmacologia , Tirosina/química , Animais , Biotina/síntese química , Biotina/química , Biotina/farmacologia , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Manganês/farmacologia , Camundongos , Conformação Molecular , Mucoproteínas , Oligopeptídeos/síntese química , Oligopeptídeos/química , Peptidomiméticos/síntese química , Peptidomiméticos/química , Proteínas Recombinantes/antagonistas & inibidores , Relação Estrutura-AtividadeRESUMO
Our continuing programme aiming at developing inhibitors of integrin α4ß7, a key mediator of various inflammatory diseases, led us to synthesise a library of cell-permeable peptides based on the biotin-R(8)ERY(∗) template, wherein the tyrosine residue has been modified by using the CuAAC reaction. The peptidomimetics were evaluated in a cell adhesion assay and shown to inhibit Mn(2+)-activated adhesion of mouse TK-1 T cells to mouse MAdCAM-1. Two of the synthesised peptidomimetics, analogues 11 and 14, are more active than our previously reported lead compound biotin-r(9)YDRREY at concentrations of 100 and 50 µM, with 14 exhibiting an IC(50) of less than 10 µM.
Assuntos
Biotina/química , Integrinas/antagonistas & inibidores , Oligopeptídeos/farmacologia , Tirosina/química , Animais , Linhagem Celular , Química Click , Relação Dose-Resposta a Droga , Camundongos , Modelos Biológicos , Estrutura Molecular , Oligopeptídeos/síntese química , Oligopeptídeos/química , Relação Estrutura-AtividadeRESUMO
Herein we report the rational design of new phosphopeptides for control of nucleation, growth and aggregation of water-soluble, superparamagnetic iron-iron oxide core-shell nanoparticles. The use of the designed peptides enables a one-pot synthesis that avoids utilizing unstable or toxic iron precursors, organic solvents, and the need for exchange of capping agent after synthesis of the NPs.