Physics And Chemistry Basis Of Biotechnology - De Cuyper - tiera.ru

Dendrimers: Chemical principles and biotechnology applications
lysine core of seven lysine units and eight arms of peptides that contain antigenic
epitopes. The overall structure of the MAP system is a polymer with a high density of
surface peptide antigens and a molecular weight greater than 10 K [90]. The almost
mutually exclusive desire to attach a large number of drug molecules to an antibody
while still retaining maximal antibody immunoreactivity may be overcome by
dendrimers which act as intermediate linkers between the drugs (capable of covalent
attachment to the dendrimer) and the antibody (which binds to the dendrimer by only
one modified site on the antibody).
A MAP dendrimer with a lipophilic surface has been synthesised for possible drug
delivery. These lipoamino acids while lipophilic also retain the solvation properties of
amino acids and peptides [91]. MAP dendrimers are peptide dendrimers which amplify
peptide immunogenicity. Unlike most vaccines, MAPS can be stored or shipped as
powders. There is an excellent review on MAPS [92]. They have been used in-vitro as
immunogens, vaccines, immunodiagnostics, serodiagnostics, ligands, inhibitors,
artificial proteins, epitope mapping, affinity purification, presentation of T-cell epitopes
and intracellular delivery. The synthesis of MAP dendrimers has been improved by the
use of a N-acetylation capping step which allows the direct (stepwise) synthesis and
purification of MAPS. The automated peptide synthesiser was programmed to provide
a N-acetylation capping reaction following each amino acid coupling reaction thus
serving as a protecting group for further reaction with unwanted amino acids in the
crude mixture [93].
3.4. BORON NEUTRON CAPTURE THERAPY
Boron neutron capture therapy is based on the nuclear reaction that occurs when a
stable B-10 isotope is irradiated with low-energy neutrons to yield high LET radiation
consisting of alpha particles and recoiling Li-7 which are energetic and cytotoxic [94].
To deliver the approximately 10 9 number of B-10 atoms needed to effectively eradicate
a tumour cell, dendrimers have been conjugated with a polyhedral borane and
subsequently attached to a monoclonal antibody. The number of boron atoms range
from 250 to 1000 per dendrimer molecule. Unfortunately, in-vivo studies with mice
revealed hepatic and splenic uptake over tumour localisation. Instead of attaching the
polyhedral borane to the periphery or surface of the dendrimer, the borane cluster has
been incorporated into the interior of the dendrimer [95]. Decaborane was reacted with
the alkyne functionality located in the interior of the dendrimer to give 0-carboranes.
The incorporation into the interior of the dendrimer increased their aqueous solubility.
An interesting application of boronated dendrimers is in electron spectroscopic
imaging-based immunocytochemistry [9G]. The dendrimers contain a boron cluster on
one side of the dendrimer and an antibody fragment on the other side. These antibodydendrimer-boranes
were used to allow the visual detection of BSA in epithelial cells of
ileum which had been internalised by endocytotic vesicles of ileal enterocytes in newborn
piglets after administration of BSA. As determined by electron spectroscopic
imaging of boron, a G4 starburst dendrimer bearing an epidermal growth factor was
bound to the cell membrane and endocytosed in-vitro of the human malignant glioma
U-343MG cell line expressing EGF receptors [97].
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