RESUMO
A series of new peptidomimetics based on the tripeptide sequence Z-Leu-Phe-Gln-OH were synthesized, with ten of these including the alpha-nitrogen atom of the N-terminal amino acid incorporated into the pyrrole cycle. The synthesized compounds were tested for antiviral activity by agar-diffusion plaque inhibition test against Coxsackievirus B1 replication in FL cell. Four of the products were observed to possess an antiviral activity, which was proven to be significant for one product. N-terminal pyrrole moiety and C-terminal free carboxyl function are available in all active compounds. On the other hand, their corresponding -OBzl and -Obu t esters are inactive.
Assuntos
Antivirais/síntese química , Antivirais/farmacologia , Materiais Biomiméticos/síntese química , Materiais Biomiméticos/farmacologia , Desenho de Fármacos , Peptídeos/química , Picornaviridae/efeitos dos fármacos , Ágar , Antivirais/química , Materiais Biomiméticos/química , Linhagem Celular , Enterovirus Humano B/efeitos dos fármacos , Enterovirus Humano B/crescimento & desenvolvimento , Glutamina/química , Humanos , Leucina/química , Fenilalanina/química , Picornaviridae/crescimento & desenvolvimento , Relação Estrutura-Atividade , Ensaio de Placa ViralRESUMO
The guanidinium group of arginine possesses a variety of biochemical functions, either by participating in direct interactions in recognition processes, or by stabilizing secondary structures. Three model compounds, selectively (17)O enriched, Ac-Arg-Ala-[(17)O]Pro-NH(2) (1), Piv-Arg-Pro-[(17)O]Gly-NH(2) (2) (C-terminal segment of the luteinizing hormone releasing hormone), and Piv-Nle-Pro-[(17)O]Gly-NH(2) (3), were prepared and studied by (17)O-nmr spectroscopy. A direct hydrogen-bonded interaction between the Arg side chain and the carbonyl main chain carboxy-terminus was found, thus confirming the tendency of Arg to participate in proton-acceptor functions.
