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Métodos Terapéuticos y Terapias MTCI
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1.
FEBS Lett ; 418(1-2): 219-23, 1997 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-9414130

RESUMEN

We describe the use of a phage-displayed random pentadecamer peptide library for searching glycosphingolipid mimicking peptides. Two phage clones (AD-1 and AD-2) were selected by biopanning using monoclonal antibody AD117m, directed to lactotetraosylceramide (Lc4Cer). The amino acid sequences of the selected clones showed high homology (VPPXFXXXY) in 9-mer. Three phage clones were selected by using monoclonal antibody H11, directed to neolactotetraosylceramide (nLc4Cer), the linkage isomer of Lc4Cer, and the displayed amino acid sequences were compared. One of these peptides showed the same amino acid sequence as that of AD-2 except for one amino acid substitution. Pentadecamer, 9-mer and point mutated 9-mer peptides were synthesized on the basis of the displayed amino acid sequences. Binding activity of the peptides to the monoclonal antibodies or Ricinus communis lectin showed that 9-mer peptides are enough to mimic the epitope carbohydrate structure. Furthermore, six of the synthesized peptides inhibited Jack bean beta-galactosidase activity towards nLc4Cer at a high concentration of the enzyme, whereas at lower enzyme concentrations some peptides showed potent activation of the enzyme activity. This is the first report of carbohydrate mimicking peptides which modulate glycosidase activity.


Asunto(s)
Ceramidas/química , Glicoesfingolípidos/química , Oligopéptidos/química , Oligopéptidos/farmacología , Biblioteca de Péptidos , beta-Galactosidasa/antagonistas & inhibidores , Secuencia de Aminoácidos , Anticuerpos Monoclonales , Bacteriófagos , Secuencia de Bases , Secuencia de Carbohidratos , Ceramidas/farmacología , Secuencia de Consenso , Fabaceae/enzimología , Glicoesfingolípidos/farmacología , Cinética , Datos de Secuencia Molecular , Oligodesoxirribonucleótidos , Lectinas de Plantas , Plantas Medicinales , Ricina/química , Ricina/farmacología , Alineación de Secuencia
2.
Nippon Ganka Gakkai Zasshi ; 98(11): 1061-6, 1994 Nov.
Artículo en Japonés | MEDLINE | ID: mdl-7825497

RESUMEN

We studied the effects and characteristics of Chinese medicines (Gorei-san (I), Saiko-keishi-to (II), Ryokei-jutsu-kan-to (III), Shokenchu-to (IV)), on the contractions (A) of bovine ciliary muscles. Ciliary muscle strips (width 4 mm x length 6 mm) were prepared and were contracted by a cholinergic agent, carbachol (10(-5)M). The 4 Chinese medicines were diluted to the concentrations of 10(-3)-10(-6) of each adult dosage per day. When these diluted medicines were added, all caused relaxations in a concentration-dependent manner. The percentages of (max B/max A) x 100 were: Gorei-san, 41 +/- 14 (%) (n = 6, mean +/- SD); Saiko-keishi-to, 37 +/- 18% (n = 6); Ryokei-jutsukan-to, 26 +/- 16% (n = 6); and Shokenchu-to, 10 +/- 5% (n = 6). Compared to the control group which did not receive Chinese medicines, drugs I, II and III showed statistically significant relaxation effects (p < 0.05). The amount of relaxation caused by these medicines (I-III) was 1/3-1/4 of the relaxation caused by a cholinergic antagonist, cyclopentlate (10(-5)M). The results suggest that Chinese medicines (I-III) produce moderate relaxation of ciliary muscles.


Asunto(s)
Cuerpo Ciliar/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Relajación Muscular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Animales , Bovinos , Músculo Liso/fisiología
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