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Solid‐phase synthesis of peptide nucleic acid (PNA) monomers and their oligomerization using disulphide anchoring linkers
Author(s) -
AldrianHerrada Gudrun,
Rabié Alain,
Wintersteiger Reinhold,
Brugidou Jean
Publication year - 1998
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/(sici)1099-1387(199806)4:4<266::aid-psc143>3.0.co;2-c
Subject(s) - chemistry , monomer , peptide nucleic acid , linker , tcep , solid phase synthesis , combinatorial chemistry , peptide , isobutyric acid , nucleic acid , residue (chemistry) , thymine , phosphine oxide , polymer chemistry , organic chemistry , stereochemistry , polymer , phosphine , biochemistry , dna , computer science , catalysis , operating system
A new simple solid‐phase method has been developed for synthesizing Boc‐protected peptide nucleic acid (PNA) monomers. An immobilized backbone 3 was built on Expansin® resin using an ester disulphide handle: 2‐hydroxypropyl‐dithio‐2′‐isobutyric acid (HPDI). The base acetic acids of thymine 5 , Z‐cytosine 9 , Z‐adenine 12 , and 6‐ O ‐benzyl guanine 17 were prepared and coupled to the immoblized backbone. The HPDI handle was cleaved under mild conditions by cyanolysis or assisted hydrolysis with tris(2‐carboxyethyl)phosphine (TCEP) to give undamaged PNA monomers. These monomers were coupled to form oligomers by solid‐phase method with another disulphide linkage: aminoethyldithio‐2‐isobutyric acid (AEDI) grafted on an amino‐functionalized TentaGel® resin, using in situ neutralization and TBTU as activating reagent. Final cleavage of the AEDI linker gave PNA bearing a cysteamide residue that could be useful for optimizing PNA properties. Oligomers of up to 16 residues long were assembled. © 1998 European Peptide Society and John Wiley & Sons, Ltd.