Tuesday, September 14, 2010
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. It provides cross-linking of various types of biomolecule using our optimized bioconjugation strategies, which have a number of applications on gene expression inhibition and related anti-sense studies.
Main Objective of Cross Linking
The main objective of cross-linking a lipid moiety to an oligonucleotide, either an oligodeoxynucleotide (ODN) or oligoribonucleotide (ORN), is to increase the hydrophobic character of the latter and its lipid-solubility. This way a conjugate would pass across the highly lipophilic cell membrane and into the cytosol, a process called transduction. Yet, depending on the lipid’s nature these conjugates may have also some other new biological properties.
Depending on the structure of the CPP and oligonucleotide moieties cross-linking can be carried out using zero-length cross-linkers and homo- or heterobifunctional linkers. Conjugation of CPPs to oligonucleotides can be made in solution or in the solid phase. Functional groups in the CPPs suitable for conjugation are amino groups from lysine, hydroxyl groups from serine and threonine, thiol groups from cysteine and carboxyl groups from aspartate and glutamate.
Cross-linking of Lipids
The conjugation process Cross-linking of lipids to oligonucleotides can usually take place at either their carbohydrate moiety, deoxyribose or ribose, or their single terminal 5’ phosphate group. Cholesterol with a spacer can be obtained by reacting the cholesteryl-chloroformate with 6-amino-1-hexanol to yield a C6 spacer linked to cholesterol by an amide bond.