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J. A. CABEZAS FERNÁNDEZ DEL CAMPO AN. R. ACAD. NAC. FARM.

Otros datos se refieren a los agentes antianémicos obtenidos por incorporación
en la molécula de derivados del polietilenglicol: «pegilación».

Palabras clave: Eritropoyetina.—EPO.—rHuEPO.—Ácido siálico.—Ácido N-ace-
tilneuramínico.—Glucocerebrosidasa.—Pegilación.

ABSTRACT

Effect of the degree of sialilation of certain drugs on their activity

Since the elucidation of the structure of the N-acetylneuraminic acid by Klenk
and Faillard in the 1950s, interest in the study of composition and characteristics
of the about 50 sialic acids (mainly N-acylneuraminics acids) currently recognized
has undergone an unceasing increase in parallel with the finding of their diverse
and important functions.

Regarding the biological role of the sialic acid component of the erythropoietin
hormone, it has been demonstrated that the concentration of this acid determines
the half-life of the hormone in blood plasma and hence the duration of the activity
of the hormone.

Furthermore, to an expansion of the half-life of the hormone, which passes
from 8 hours to about one week, corresponds to an increase in the content of this
acid in the composition of the hormone molecule (this increase being achieved
by recombinant techniques). This expansion allows a remarkable advantage in the
administration procedure of this drug to people who require it for their antianaemic
treatment (renal disorders and immunodeficient patients as well as persons
subjected to chemotherapy).

Curiously, the desialilated erythropoietin keeps its activity in in vitro but not in
in vivo assays.

Parallel studies, although not as deep as these, have also been carried out with
other sialoglycoproteins and with the cerebrosidase enzyme, as well as other
polyethylene glycol (PEG) derivatives.

Key words: Erythropoietin.—EPO.—rHuEPO.—Sialic acid.—N-acetylneura-
minic acid.—Glucocerebrosidase.—Pegylation.

1. INTRODUCCIÓN: HIPÓTESIS

1.ª) ¿Influye per se la molécula del ácido siálico (integrante de
la fracción oligosacarídica del glicoconjugado), como constituyente
de la composición de un medicamento de naturaleza glicoconjugada,
en la actividad de éste?

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