Resistance of morpholino phosphorodiamidate oligomers to enzymatic degradation.
Oligomers possessing the Morpholino phosphorodiamidate backbone were evaluated for resistance to a variety of enzymes and biologic fluids. A 25-mer was incubated with nucleases, proteases, esterases, and serum, and the reaction mixtures were directly analyzed by MALDI-TOF mass spectrometry. The 25-mer was completely resistant to 13 different hydrolases and serum and plasma. The excellent resistance of Morpholino phosphorodiamidates to enzymatic attack indicates their suitability for in vivo use.
Hudziak
R M
RM
ANTIVIRALS, Inc., Corvallis, OR 97333, USA.
Barofsky
E
E
Barofsky
D F
DF
Weller
D L
DL
Huang
S B
SB
Weller
D D
DD
D001790:Blood Physiological Phenomena; D003851:Deoxyribonucleases / Q000737:chemistry; D004355:Drug Stability; D010450:Endopeptidases / Q000737:chemistry; D004950:Esterases / Q000737:chemistry; D006867:Hydrolases / Q000737:chemistry*; D013058:Mass Spectrometry; D015394:Molecular Structure; D009025:Morpholines / Q000737:chemistry*; D010755:Organophosphates / Q000737:chemistry*; D010949:Plasma / Q000502:physiology*; D012260:Ribonucleases / Q000737:chemistry
D009025:Morpholines; D010755:Organophosphates; D006867:Hydrolases; D003851:Deoxyribonucleases; D004950:Esterases; D012260:Ribonucleases; D010450:Endopeptidases