DNA-encoded synthesis

The mitochondria also contain small quantities of DNA, as well as RNA and ribosomes. Mitochondrial DNA encodes the synthesis of certain specific inner cell membrane proteins. Mitochondria can also divide during cell replication. 

Efremenko, E.N., Votchitseva, Yu.V., Aliev, T.K., and Varfolomeyev, S.D. (2005) Recombinant plasmid DNA pTES-His-OPH encoding synthesis of polypeptide with properties of organophosphate hydrolase, and strain E.coli - producer of polypeptide with properties of organophosphate hydrolase. Patent RU 2255975. 

DNA-Templated Organic Synthesis. An exciting recent concept developed largely by Liu and co-workers is DNA-templated organic synthesis. DNA-templated synthesis generates products individually linked to ODNs that encode and direct their synthesis. DNA-templated synthesis is limited by the fact that DNA-linked reagents need to be prepared, reactions need to be... 

Genetic information flows from DNA to RNA to protein. DNA encodes the information required for synthesis of proteins and a copy of the encoded information is transcribed and processed into messenger RNA (mRNA). The information carried by the mRNA directs the synthesis of proteins, this process is called translation. Translation takes place on the surface of particles called ribosome s. 

The arrangement of base triplets on DNA encodes genetic information by dictating the synthesis of proteins. 

The DNA strands were first reported by Brenner and co-workers to define the sequence of a peptide constructed on a solid support. Upon completion of the synthesis, an on-bead assay was performed. Whereas each bioactive peptide was defined by a unique DNA sequence, the decoding process simply involved amplification of the code by the polymerase chain reaction followed by sequencing. This technique marked the beginning of the tagging method for encoded split synthesis. Sequenceable peptide strands are an alternative to DNA encoding. The code is read by HPLC of the Edmon degradation phenylthiohydantoin amino acid derivatives, a well-developed microsequencing method. 

Discovery of the structure of DNA in 1953 and subsequent elucidation of how DNA directs synthesis of RNA, which then directs assembly of proteins—the so-called central dogma—were monumental achievements marking the early days of molecular biology. However, the simplified representation of the central dogma as DNA—>RNA— protein does not reflect the role of proteins in the synthesis of nucleic acids. Moreover, as discussed in later chapters, proteins are largely responsible for regulating gene expression, the entire process whereby the information encoded in DNA is decoded into the proteins that characterize various cell types. 

Mitochondrial RNA Polymerase The RNA polymerase that transcribes mtDNA is encoded in nuclear DNA. After synthesis of the enzyme in the cytosol, it is Imported into the mitochondrial matrix by mechanisms described in Chapter... 

There are two types of nucleic acids—deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). DNA encodes an organism s hereditary information and controls the growth and division of cells. In most organisms the genetic information stored in DNA is transcribed into RNA. This information can then be translated for the synthesis of all the proteins needed for cellular stracture and function. 

DNA encodes the information needed to make proteins in the form of triplets of bases (codons), for example thymine-adenine-cytosine (TAG) in the diagram below. As RNA is synthesized from DNA, these are turned into complementary codons (in the example below, AUG) by pairing up the bases as shown on p. 1138. This RNA forms the instructions for protein synthesis by the ribosome—perhaps the most elaborate molecular structure in the known universe. Each codon of the RNA chain tells the ribosome to add a specific amino acid to the growing protein. For example, the codon AUG indicates methionine, which we met as a component of SAM. Methionine is a typical amino acid of the kind present in proteins, but is also the starter unit of all proteins. 

Transcription (Making RNA from DNA) DNA contains genes that encode proteins, starting with a start codon and ending with a stop codon. In a process called transcription, the cell uses DNA to create RNA that reflects the information contained in that DNA strand. Transcription occurs in the nucleus (when one exists in the cell). This copy of the DNA strand is called messenger RNA (mRNA), which eventually directs the synthesis of the protein the DNA encodes. 

A spht-pool approach has been used to prepare a hbrary of 800000000 DNA-encoded small molecules (see Scheme 1.8 for an example for a synthesis of a DNA-encoded hbrary). After each diversification step, the small molecules were derivatised with a DNA tag to encode the substituent that had been added. At the end of the synthesis, the small molecules - each of which was... 

Scheme 1.8 Synthesis of a DNA-encoded small-molecule library. The DNA tag is not drawn to scale. Reagents and conditions. (1) (a) attach DNA tag (b) acylation with Fmoc-protected amino acid (c) purify (d) deprotect (2) (a) attach DNA tag (b) cyanuric chloride (c) substitute with R% NH (3) (a) attach DNA tag (b) substitute with R R NH (c) purify (4) ligate primer.

In this chapter, we will first discuss the basic principles of DNA-templated organic synthesis, as it is the mechanistic foundations for DNA-encoded libraries then we will discuss the progressive development of DNA-templated libraries and the evolution into a novel drug discovery tool. We will also discuss the DNA-recorded library, which also encodes library molecules with DNA but is conceptually different. These discussions will naturally involve specific drug discovery programs in which these libraries were applied and finally, we will discuss the outlook of DNA-eneoded libraries in the future of drug discovery. 

Our focus in this chapter is the DNA-encoded library as a tool in exploring chemical space for drug discovery. For the applications of DNA-templated synthesis in other fields, such as the origin of life, biodetection, nano-technol-ogy, etc., we refer readers to various excellent reviews. ... 

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