SYNTHESIS AND ENZYMATIC STABILITY OF PHOSPHODIESTER-LINKED PEPTIDE - OLIGONUCLEOTIDE HYBRIDS

Nucleopeptides Ac-Tyr(p(3')dACGT)-Ala-Phe-Gly-NH2, Ac-Thr(p(3')dACGT)- Ala-Phe-Gly-OH, Ac-Ser(p(3')dACGT)-Ala-Phe-Gly-OH, and Phac-Hse(p(3')d ACGT)-Ala-Phe-Gly-OH, in which the 3'-end of a tetradeoxyribonucleotid e is linked by a phosphodiester bond to a hydroxylated amino acid, wer e synthesized using a stepwise solid-phase methodology to study the in fluence of the linking amino acid on their stability to 3'-exonuclease s. HPLC analysis of the reaction crudes after treatment of each nucleo peptide with snake venom phosphodiesterase showed that the lability of the amino acid-nucleoside linkage increases in the order Thr < Ser < Hse < Tyr.