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Gene synthesis

  • Conference paper
  • First Online:
Bioprocesses Including Animal Cell Culture

Part of the book series: Advances in Biochemical Engineering/Biotechnology ((ABE,volume 37))

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Abstract

The scope of this review is to show the impact of chemistry on the biological sciences by presenting the basic concepts of oligonucleotide chemistry underlying gene synthesis. We demonstrate the P(III) and P(V) chemistry for chain elongation, then continue with the isolation and characterisation of synthetic oligonucleotides. The applications of oligonucleotides as tools for gene isolation, detection of genetic diseases, and site specific mutagenesis will be touched upon only in a few examples. But we review in detail the more powerful applications: the combination of synthetic oligonucleotides into double-stranded gene fragments and genes. Genes are either synthesized by the classical Khorana approach, by making use of DNA polymerase or some other specialized methods. Their design is discussed with the implications of secondary structure as well as retrosynthetic considerations. Furthermore, considerations concerning the mutagenesis of genes as well as their mode of expression including synthetic control units are outlined.

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Abbreviations

aa:

amino acid

AMV:

avian mycloblastosis virus

Ap:

ampicillin

B:

nucleotide base

bp:

base pairs

cDNA:

complementary DNA

CPG:

controlled pore glass

DBU:

1.5-diazabicyclo-[5.4.0]-undec-5-ene

DCC:

dicyclohexylcarbodiimide

DMT:

4,4′-dimethoxytrityl

dNTP:

deoxynucleotide triphosphate

Β-gal:

Β-galactosidase

HPLC:

high performance liquid chromatography

IFN:

interferon

IPTG:

isopropyl-Β-D-thiogalactopyranoside

kb:

kilo base(s)

lac PO:

lac promoter-operator

N:

any nucleoside

nt:

nucleotide(s)

ori:

origin of replication

P:

promotor

p:

plasmid

PAA:

polyacrylamide

PAGE:

polyacrylamide-gel electrophoresis

Pu:

purine

Py:

pyrimidine

r:

(superscript) resistence

RBS:

ribosome binding site

RP:

reversed phase

s:

(supercript) sensitivity

SD:

Shine Dalgarno-sequence

ss-DNA:

single-stranded DNA

stp:

stop codon

t:

terminator

tlc:

thin layer chromatography

Tc:

tetracycline

TMV:

tobacco mosaic virus

wt:

wild type

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  1. Institut f. Org. Chemie, University of Frankfurt, Niederurseler Hang, D-6000, Frankfurt 50, Germany

    Joachim Engels

  2. Hoechst AG, D-6230, Frankfurt/M. 80, Germany

    Eugen Uhlmann

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Engels, J., Uhlmann, E. (1988). Gene synthesis. In: Bioprocesses Including Animal Cell Culture. Advances in Biochemical Engineering/Biotechnology, vol 37. Springer, Berlin, Heidelberg. https://doi.org/10.1007/BFb0009178

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