Bioconjugation

Bioconjugation

Advances in peptides and nucleic acids synthesis, areas where Bio Synthesis has over twenty years of experience, have promoted the development of bioconjugates where these molecules are either cross-linked to each other or to other compounds to yield products with distinct properties. Bio Synthesis, benefiting of its expertise in peptides and nucleic acids synthesis, is developing new methods for the efficient production of bioconjugates.

Bioconjugates

Taking advantage of its expertise in nucleic acids and peptide synthesis, BioSynthesis is developing new approaches for the production of different bioconjugates. From the point of view of therapeutic applications, because of their potential uses in genetic therapy and blocking gene expression the bioconjugates of nucleic acids are the most important ones.

Properties of Bioconjugates

In general these bioconjugates acquire new properties, such as resistance to degradation and passage of the hydrophilic and anionic oligonucleotide across the hydrophobic negatively charged cell membrane or transduction. Yet, a suitable bioconjugate should maintain practically all of the oligonucleotide’s biological properties.

Oligonucleotide moiety of Bioconjugate

This moiety or cargo of the bioconjugate can be either a DNA/ODN or a RNA/ORN. Because of their anionic nature they cannot pass across cell membranes unless they are conjugated to a CPP. Peptide-DNA conjugates are used in genetic therapy to replace a defective gene or alternatively to inhibit the expression of a specific gene by antisense DNA.

Use of Bioconjugates in Apoptosis

Use of Bioconjugates in Apoptosis

Bioconjugation Service: In some cases the carrier moiety can be a synthetic polymer such as poly-L-glutamic acid to which the drug paclitaxel has been conjugated. The actual mechanism of action is still being elucidated. Another carrier that has been used successfully are the cyclodextrins to which small pro-apoptotic agents can be linked. For example For instance a conjugate of anti-CD33 antibody and the amphipathic peptide KLA target efficiently CD33-positive myeloid leukemia cell lines to cause their apoptotic death induced by the D-(KLAKLAK)2 proapoptotic peptide.

Bioconjugates: The study of apotosis, the programmed death of cells, has direct applications to cancer a disease where tumor cells have developed mechanisms to avoid it and multiply without control. The fact that apoptosis is usually mediated by some cell receptors makes conjugates a valuable tool in elucidating apoptosis’ mechanisms as well drug development.

Bioconjugations: Cells over-expressing erbB2 and resistant to apoptosis can be killed more efficiently by a conjugate composed of an erbB2-binding heptapeptide conjugated to the proapoptotic a-tocopheryl succinate (a-TOS) rather than the unconjugated a-TOS. Use of the conjugate resulted in breast carcinomas in a breast cancer prone transgenic mouse strain. Recently it has been shown that conjugates of cytochrome c and oligoarginine linked by a thioether resulted in an increased entry into the cell, compared to cyt. c alone, and increase in apoptotic activity. In contrast a conjugate linked by a disulfide bond although entered into the cell did not enhance the apoptotic activity.