[3-(1,4-Cyclohexadienyl)-L-alanine,8-lysine]vasopressin: synthesis and some pharmacological properties.
J Med Chem
; 22(12): 1487-92, 1979 Dec.
Article
en En
| MEDLINE
| ID: mdl-536993
[3-(1,4-Cyclohexadienyl)-L-alanine,8-lysine]vasopressin, otherwise known as [3-(2,5-dihydrophenylalanine),8-lysine]vasopressin or [DiHPhe3]lysine-vasopressin, has been synthesized in an attempt to utilize 2,5-dihydrophenylalanine (DiHPhe) to evaluate the contribution of aromaticity in position 3 to biological activity. The analogue has the same primary structure as lysine-vasopressin, except that two additional hydrogen atoms are present on the ring moiety of the phenylalanine residue in position 3. The key intermediate was the protected nonapeptide N-carbobenzoxy-S-benzyl-L-cysteinyl-L-tyrosyldihydrophenyl-L-alanyl-L-glutaminyl-L-asparaginyl-S-benzyl-L-cysteinyl-L-prolyl-N epsilon-tosyl-L-lysylglycinamide that was synthesized stepwise by the solid-phase technique. Deprotection with sodium in liquid ammonia was followed by sulfhydryl oxidation with I2 to give the hormone analogue. [DiHPhe3]lysine-vasopressin exhibited 125--130 units/mg of antidiuretic, 129--132 units/mg of rat pressor, and 6 units/mg of rat uterus contracting activity. To confirm the presence of DiHPhe in the analogue, an enzymatic procedure employing Aspergillus oryzae was developed that liberates in high yield the amino acid residue in position 3 of the posterior pituitary hormone structure. This study should be applicable to other biologically active peptides.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Lipresina
Límite:
Animals
Idioma:
En
Revista:
J Med Chem
Asunto de la revista:
QUIMICA
Año:
1979
Tipo del documento:
Article
Pais de publicación:
Estados Unidos