TY - JOUR
T1 - LNA guanine and 2,6-diaminopurine. Synthesis, characterization and hybridization properties of LNA 2,6-diaminopurine containing oligonucleotides
AU - Rosenbohm, C.
AU - Pedersen, Daniel Sejer
AU - Frieden, M.
AU - Jensen, F.R.
AU - Koch, T.
AU - Arent, S.
AU - Larsen, S.
PY - 2004/5/1
Y1 - 2004/5/1
N2 - LNA guanine and 2,6-diaminopurine (D) phosphoramidites have been synthesized as building blocks for antisense oligonucleotides (ON). The effects of incorporating LNA D into ON were investigated. As expected, LNA D containing ON showed increased affinity towards complementary DNA (ΔT +1.6 to +3.0°C) and RNA (ΔT +2.6 to +4.6°C) ON. To evaluate if LNA D containing ON have an enhanced mismatch sensitivity compared to their complementary LNA A containing ON thermal denaturation experiments towards singly mismatched DNA and RNA ON were undertaken. Replacing one LNA A residue with LNA D, in fully LNA modified ON, resulted in higher mismatch sensitivity towards DNA ON (ΔΔT -4 to >-17°C). The same trend was observed towards singly mismatched RNA ON (ΔΔT D-a = -8.7°C and D-g = -4.5°C) however, the effect was less clearcut and LNA A showed a better mismatch sensitivity than LNA D towards cytosine (ΔT +5.5°C). © 2004 Elsevier Ltd. All rights reserved.
AB - LNA guanine and 2,6-diaminopurine (D) phosphoramidites have been synthesized as building blocks for antisense oligonucleotides (ON). The effects of incorporating LNA D into ON were investigated. As expected, LNA D containing ON showed increased affinity towards complementary DNA (ΔT +1.6 to +3.0°C) and RNA (ΔT +2.6 to +4.6°C) ON. To evaluate if LNA D containing ON have an enhanced mismatch sensitivity compared to their complementary LNA A containing ON thermal denaturation experiments towards singly mismatched DNA and RNA ON were undertaken. Replacing one LNA A residue with LNA D, in fully LNA modified ON, resulted in higher mismatch sensitivity towards DNA ON (ΔΔT -4 to >-17°C). The same trend was observed towards singly mismatched RNA ON (ΔΔT D-a = -8.7°C and D-g = -4.5°C) however, the effect was less clearcut and LNA A showed a better mismatch sensitivity than LNA D towards cytosine (ΔT +5.5°C). © 2004 Elsevier Ltd. All rights reserved.
UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-1842666864&partnerID=8YFLogxK
U2 - 10.1016/j.bmc.2004.02.008
DO - 10.1016/j.bmc.2004.02.008
M3 - Journal article
C2 - 15080935
SN - 0968-0896
VL - 12
SP - 2385
EP - 2396
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 9
ER -