RESUMO
We present the finding of a dimeric ACE2 peptide mimetic designed through side chain cross-linking and covalent dimerization. It has a binding affinity of 16 nM for the SARS-CoV-2 spike RBD, and effectively inhibits the SARS-CoV-2 pseudovirus in Huh7-hACE2 cells with an IC50 of 190 nM and neutralizes the authentic SARS-CoV-2 in Caco2 cells with an IC50 of 2.4 µM. Our study should provide a new insight for the optimization of peptide-based anti-SARS-CoV-2 inhibitors.
Assuntos
Antivirais/farmacologia , Fragmentos de Peptídeos/farmacologia , Peptidomiméticos/farmacologia , SARS-CoV-2/efeitos dos fármacos , Sequência de Aminoácidos , Enzima de Conversão de Angiotensina 2/química , Antivirais/síntese química , Antivirais/metabolismo , Linhagem Celular Tumoral , Humanos , Testes de Sensibilidade Microbiana , Fragmentos de Peptídeos/síntese química , Fragmentos de Peptídeos/metabolismo , Peptidomiméticos/síntese química , Peptidomiméticos/metabolismo , Ligação Proteica , Domínios Proteicos , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/metabolismoRESUMO
A series of cyclic Arg-rich mitochondria-penetrating peptides were prepared with variation in the macrocycle size and the chirality of Arg residues. A cyclic heptapeptide was demonstrated to be an efficient mitochondria-specific delivery vector for delivering membrane impermeable peptides.
Assuntos
Membrana Celular/metabolismo , Peptídeos Penetradores de Células/metabolismo , Mitocôndrias/metabolismo , Membrana Celular/química , Sobrevivência Celular , Peptídeos Penetradores de Células/química , Ciclização , Células HeLa , Humanos , Mitocôndrias/química , Conformação MolecularRESUMO
A new robust strategy was reported for the epimerization-free synthesis of C-terminal Cys-containing peptide acids through mercaptoethanol-mediated hydrolysis of peptide thioesters prepared in situ from peptide hydrazides. This simple-to-operate and highly efficient method avoids the use of derivatization reagents for resin modification, thus providing a practical avenue for the preparation of C-terminal Cys-containing peptide acids.