An efficient, convenient solid-phase synthesis of amino acid-modified peptide nucleic acid monomers and oligomers

Bioconjugate Chemistry
Baghavathy S BalajiMichael R Lewis

Abstract

An efficient and highly versatile method for the synthesis of amino acid-modified peptide nucleic acid (PNA) monomers is described. By using solid-phase Fmoc techniques, such monomers can be assembled readily in a stepwise manner and obtained in high yield with minimal purification. Protected neutral hydrophilic, acidic, and basic amino acids were coupled to 2-chlorotrityl chloride resin. Following Fmoc removal, innovative conditions for the key step, reductive alkylation with N-Fmoc-aminoacetaldehyde, were developed to circumvent problems encountered with previously reported methods. Activation and coupling of pyrimidine and purine nucleobases to the resulting secondary amines afforded amino acid-modified PNA monomers. The mild reaction conditions utilized were compatible with sensitive and labile functional groups, such as tert-butyl ethers and tert-butyl esters. PNA monomers were obtained in 36-42% overall yield and very high purity, after cleavage and purification. Using standard solid-phase Fmoc chemistry, two of these monomers were incorporated with high coupling efficiency into a variety of modified PNA oligomers, including four tetradecamers designed to target bcl-2 mRNA. Such modified oligomers have the potential to en...Continue Reading

References

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Oct 14, 2003·Journal of Peptide Science : an Official Publication of the European Peptide Society·Robert Sheppard
Mar 17, 2005·Bioconjugate Chemistry·Xiankai SunJohn-Stephen Taylor

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Citations

Aug 21, 2007·Expert Opinion on Biological Therapy·Soccorsa PensatoAlessandra Romanelli
Apr 14, 2010·Molecular BioSystems·Wei HeCatalina Achim
Sep 3, 2014·Biotechnology, Biotechnological Equipment·Elena GeorgievaGanka Chaneva
Feb 22, 2008·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Fang JiaMichael R Lewis
Jul 3, 2021·Biopolymers·Sriram KumarRebecca E Taylor

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