RESUMEN
Five angiotensin cycloanalogues have been synthesised by classical methods of peptide chemistry, cyclisation being carried out via pentafluorophenyl esters. Cycloanalogues (I-IV) with a fixed potential turn in the C-terminal part of the angiotensin molecule inferred on the basis of physico-chemical data do not possess angiotensin-like activity. Compounds (V) with enlarged cycle shows decreased pressor effects as compared with angiotensin. By means of circular dichroism chiroptical properties of the compounds in water and ethanol were examined.
Asunto(s)
Angiotensina II/análogos & derivados , Péptidos Cíclicos/síntesis química , Secuencia de Aminoácidos , Angiotensina II/análisis , Angiotensina II/síntesis química , Angiotensina II/farmacología , Animales , Presión Sanguínea/efectos de los fármacos , Fenómenos Químicos , Química , Dicroismo Circular , Técnicas In Vitro , Datos de Secuencia Molecular , Contracción Muscular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Péptidos Cíclicos/análisis , Péptidos Cíclicos/farmacología , RatasRESUMEN
Linear and cyclic analogues of angiotensin were studied to clarify the structural properties of peptides possessing a histamine-releasing action. It was shown that an increase in the angiotensin basicity or its cyclization leads to the appearance of the histamine-releasing activity which is not characteristic of the natural hormone. This increase in the basicity of the angiotensin cyclic analogs results in highly active compounds with the EC50 exceeding by 2 to 3 orders of magnitude that of polymyxin B or substance 48/80. The data obtained confirm the hypothesis postulating a high degree of amphiphilicity for histamine-releasing peptides. As a result of cyclization of angiotensin analogues, a block of positively charged amino acids with an oppositely located hydrophobic region is formed. This finding can be of importance for the effective interaction of peptides with cellular structures as well as for the stimulation of secretory processes.
Asunto(s)
Angiotensina II/farmacología , Liberación de Histamina/efectos de los fármacos , Mastocitos/metabolismo , Péptidos Cíclicos/farmacología , Hormona Adrenocorticotrópica/farmacología , Secuencia de Aminoácidos , Angiotensina II/análogos & derivados , Animales , Bradiquinina/farmacología , Concanavalina A/farmacología , Calidina/farmacología , Datos de Secuencia Molecular , Neurotensina/farmacología , Cavidad Peritoneal/citología , Polimixina B/farmacología , Conformación Proteica , Ratas , Sustancia P/farmacología , p-Metoxi-N-metilfenetilamina/farmacologíaRESUMEN
Biological properties of five novel angiotensin analogues synthesized, using the conventional methods of peptide chemistry, have been studied. Cyclization was attained by means of amide linkage with the aid of diphenylphosphorylazide or pentafluorophenyl esters. Unlike the natural hormone, the cyclic analogues of angiotensin show no pressor activity, but elicit a depressor effect untypical of angiotensin. A slight pressor activity was exhibited by the compound containing aspartic acid in position 1. The cyclic analogues in question release histamine from peritoneal mast cells in rats.
Asunto(s)
Angiotensina II/análogos & derivados , Péptidos Cíclicos/síntesis química , Aldosterona/biosíntesis , Angiotensina II/síntesis química , Angiotensina II/farmacología , Animales , Presión Sanguínea/efectos de los fármacos , Fenómenos Químicos , Química , Relación Dosis-Respuesta a Droga , Femenino , Liberación de Histamina/efectos de los fármacos , Técnicas In Vitro , Masculino , Péptidos Cíclicos/farmacología , RatasRESUMEN
The synthesis and biological properties of 10 angiotensin cyclic analogues are described. These compounds exhibit prolong depressor effects and act as potent histamine-releasing agents.
Asunto(s)
Angiotensina II/análogos & derivados , Antihipertensivos , Liberación de Histamina/efectos de los fármacos , Péptidos Cíclicos/farmacología , Angiotensina II/síntesis química , Angiotensina II/farmacología , Animales , Antihipertensivos/síntesis química , Péptidos Cíclicos/síntesis química , RatasRESUMEN
A model involving quasicyclization of protein molecules following the stepwise reactions of limited proteolysis was developed. On the basis of the model new active sites were detected in immunoglobulins of various species as well as chemical synthesis of the sites was carried out. The new group of the substances was designated as immunopoietins. The primary structure of various species immunoglobulins was analyzed and evolutional stability of the immunopoietin structure was shown.
Asunto(s)
Fragmentos de Inmunoglobulinas/análisis , Inmunoglobulina G/análisis , Secuencia de Aminoácidos , Animales , Humanos , Especificidad de la Especie , Timopoyetinas/análisisRESUMEN
The binding of angiotensin II and its analogues (13) to rabbit antibodies and glomerular cell receptors from rat adrenal cortex was studied, using the radioimmunoassay method and radioreceptor analysis. Double modifications introduced into the angiotensin structure were found to increase in an additive fashion its binding to the antibodies and renal cell receptors. The relative binding activity of the analogues carrying a double modification can be assessed if the activities of the analogues with the appropriate single modifications are known. It was concluded that the testing of modifications in the peptide structure for their additivity may provide some insight into the conformational properties of peptides during their binding to the protein.
Asunto(s)
Corteza Suprarrenal/metabolismo , Angiotensina II/metabolismo , Anticuerpos/metabolismo , Receptores de Angiotensina/metabolismo , Receptores de Superficie Celular/metabolismo , Angiotensina II/análogos & derivados , Animales , Sitios de Unión de Anticuerpos , Técnicas In Vitro , Cinética , Modelos Biológicos , Conformación Proteica , Conejos/inmunología , Radioinmunoensayo , Ensayo de Unión Radioligante , RatasRESUMEN
Conventional methods of peptide chemistry have been used to synthesize the C-terminal nonapeptide from human immunoglobulin E, which is a potential cytophilic binding site of the IgE molecule responsible for its primary recognition and binding to specific target cell receptors.
Asunto(s)
Inmunoglobulina E/síntesis química , Fragmentos de Inmunoglobulinas/síntesis química , Fragmentos de Péptidos/síntesis química , Secuencia de Aminoácidos , HumanosRESUMEN
Low-molecular fragments of immunoglobulins IgG-(245-349) (Glu-Pro-Gln-Val-Tyr), IgM-(451-455) (Arg-Pro-Asp-Val-Tyr), IgA-(347-351) (Arg-Pro-Glu-Val-His), and IgE-(430-435) (Ala-Ala-Pro-Glu-Val-Tyr), potentially active immunoregulators of a novel type, have been synthesised by classical methods of peptide chemistry. This group of compounds, which in biological effects are similar to thymopoietin, was given the name of immunopoietins.