What are Oligomimetics or oligo-nucleotide mimetics?
Oligomimetics are chemically modified compounds designed to mimic the action of naturally occurring molecules. Correctly designed oligomimetics are chemically-modified DNA and RNA molecules which exhibit enhanced stability, bioavailability, specificity and efficacy. This makes oligomimetics excellent candidates for use in clinical applications such as genetic diagnostics, therapeutics, DNA based diagnostics as well as in chip technologies.
Synthetic DNA and RNA oligonucleotides and their analogues have become important research tools in chemistry, biology and biochemistry during recent decades. The great potential of these compounds for various therapeutic applications such as antisense, antigene and ribozyme-based reagents has intensified research to more thoroughly investigate the chemistry and biochemistry of these compounds. The use of modified oligonucleotides or oligomimetics has allowed the development of powerful research tools for efficient regulation of gene expression and gene functions, both in vitro and in vivo.
The term “mimic” means to imitate or simulate. Similarly the term “mimetic” also means “to imitate”. According to the Encyclopaedia Britannica the term MIMETIC originates from the Late Latin word mimeticus, from Greek mimētikos, and from mimeisthai to imitate, or from mimos meaning mime. Its first known use was in 1637. For a chemical compound this means that a mimic compound has a similar structure, action, or effect. Hence, an oligomimetic is a modified oligonucleotide that can mimic or imitate the original oligonucleotide.
Desired properties of oligomimetics are improved thermal stability of their duplexes and triplexes, hydrolytic resistance to cellular nucleases and biological activity in in-vitro and in-vivo systems.
Oligomimetics may consist of nucleic acid building blocks, made of either natural or modified nucleotides, include fluorescent markers, dyes and other modifications. The design and synthesis of oligomimetics to achieve optimal biochemical and structural properties involves the use of modified building blocks such as 3'-modified oligonucleotide N3'-->P5' phosphoramidates, analogues with modifications at the 2'-position of nucleoside sugar rings, the use of bridged nucleic acids, such as 2’4’-bridged or 2',4'-BNANC (2'-O,4'-aminoethylene bridged) nucleic acids, or combinations of them.
The bridged nucleic acid 2',4'-BNANC (2'-O,4'-aminoethylene bridged nucleic acid) is a compound containing a six-member bridged structure with an N-O linkage.
Egli M, Gryaznov SM; Synthetic oligonucleotides as RNA mimetics: 2'-modified Rnas and N3'-->P5' phosphoramidates. Cell Mol Life Sci. 2000 Sep;57(10):1440-56.