Page 44 - 66_03

TOMÁS GIRBÉS JUAN ANAL. REAL ACAD. FARM.

Palabras clave: Proteínas inactivadoras de ribosomas.- RIPs.- Síntesis de proteínas.-
Inmunotoxinas.- Cáncer.

SUMMARY

Ribosome-Inactivating proteins (RIPs) and their aplication in the construction of
immunotoxins for the experimental therapy of cancer.

The ribosome –inactivating proteins (RIPs) are protein synthesis inhibitors
that trigger the irreversible inactivation of ribosomes. The most known RIPs are those
from plants being ricin the most studied one. The molecular mechanism of action of
RIPs is the depurination of the largest rRNA (28 S rRNA in mammalian). RIPs act also
on other substrates like DNA, viral genomic RNA and some synthetic polynucleotides
which become multidepurinated. Some RIPs display antiviral activity on plant and
animal viruses and also have a topological activity on double stranded DNA. We have
found a novel kind of RIP that we named non-toxic type 2 RIP. Among these RIPs are
nigrin and basic nigrin b from Sambucus nigra and ebulin from Sambucus ebulus. The
new RIPs are between 1.000 and 10.000 times less toxic for cultured human cells and
mice than ricin. The most noteworthy application of RIPs is the construction of
conjugates and immunotoxins for the experimental therapy of human cancer. We have
prepared conjugates active on colon cancer cells and immunotoxins active on CD105+
cells which are characteristic of the tumoral neovasculature.

Key words: Ribosome-inactivating proteins.- RIPs.- Protein synthesis.- Immunotoxins.-
Cancer.

Excmo. Sr. Director de la Real Academia de Farmacia,
Excmas. Sras. Académicas, Excmos. Sres. Académicos, señoras y
señores, es para mi un gran honor ser admitido en la Real Academia de
Farmacia y poder dirigirme hoy a todos ustedes. Quiero agradecer en
primer lugar al Profesor D. Manuel Ruiz Amil Catedrático de Bioquímica
y Biología Molecular y amigo, el haberme propuesto a esta institución
como académico correspondiente y en segundo lugar el haber presentado
mi curriculum de la manera tan generosa con que lo ha hecho. Agradezco
asimismo a los Profs. D. Antonio Portolés Alonso y D. Juan Tamargo
Menéndez el haber apoyado la propuesta del Prof. Ruiz Amil. Tengan la
seguridad de que haré lo posible para no defraudarles y espero ser digno
del honor que se me hace.

2