Synthesis and enzymatic stability of phosphodiester-linked peptide-oligonucleotide hybrids.
Nucleopeptides Ac-Tyr(p3' dACGT)-Ala-Phe-Gly-NH2, Ac-Thr(p3'dACGT)-Ala-Phe-Gly-OH, Ac-Ser(p3'dACGT)-Ala-Phe-Gly-OH, and Phac-Hse(p3'dACGT)-Ala-Phe-Gly-OH, in which the 3'-end of a tetradeoxyribonucleotide is linked by a phosphodiester bond to a hydroxylated amino acid, were synthesized using a stepwise solid-phase methodology to study the influence of the linking amino acid on their stability to 3'-exonucleases. HPLC analysis of the reaction crudes after treatment of each nucleopeptide with snake venom phosphodiesterase showed that the lability of the amino acid-nucleoside linkage increases in the order Thr < Ser < Hse < Tyr.
Robles
J
J
Departament de Química Orgànica, Facultat de Química, Universitat de Barcelona, Spain.
Maseda
M
M
Beltrán
M
M
Concernau
M
M
Pedroso
E
E
Grandas
A
A
D000469:Alkaline Phosphatase / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D004952:Esters / Q000378:metabolism; D006868:Hydrolysis; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000378:metabolism*; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000378:metabolism*; D043264:Phosphodiesterase I; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*
D004952:Esters; D009841:Oligonucleotides; D009842:Oligopeptides; D000469:Alkaline Phosphatase; D010727:Phosphoric Diester Hydrolases; D043264:Phosphodiesterase I; C470790:phosphodiesterase I, snake venom