FFAME.org :: Myong Kim's Publications

Synthesis of pyrophosphates for in vitro selection of catalytic RNA molecules
Kim, HJ Kim, MJ Karalkar, N Hutter, D Benner, SA
Nuc. Nuc. Nuc. acids 27 43-56 (2008)

Synthesis of a novel bicyclic nucleoside with a 3,7-anhydrooctofuranosyl skeleton
Kim, MJ Chun, MW
Aust. J. Chem. 60 (4) 291-295 (2007)
<Abstract>

We have developed an efficient route for the synthesis of a novel bicyclic nucleoside using a key intermediate 13, which was prepared from 1,2: 5,6-di-O-isopropylidene-alpha-D-glucose. 1,2-Nucleophilic addition of aldehyde 8 with allyltrimethylsilane and intramolecular Williamson reaction were successfully achieved to synthesize an intermediate with a 3,7-anhydrooctofuranosyl skeleton.

Orthogonal activation of the reengineered A(3) adenosine receptor (neoceptor) using tailored nucleoside agonists
Gao, ZG Duong, HT Sonina, T Kim, SK Van Rompaey, P Van Calenbergh, S Mamedova, L Kim, HO Kim, MJ Kim, AY Liang, BT Jeong, LS Jacobson, KA
J. Med. Chem. 49 (9) 2689-2702 (2006)
<Abstract>

An alternative approach to overcome the inherent lack of specificity of conventional agonist therapy can be the reengineering of the GPCRs and their agonists. A reengineered receptor ( neoceptor) could be selectively activated by a modified agonist, but not by the endogenous agonist. Assisted by rhodopsin-based molecular modeling, we pinpointed mutations of the A(3) adenosine receptor (AR) for selective affinity enhancement following complementary modifications of adenosine. Ribose modifications examined included, at 3' : amino, aminomethyl, azido, guanidino, ureido; and at 5' : uronamido, azidodeoxy. N-6-Variations included 3-iodobenzyl, 5-chloro-2-methyloxybenzyl, and methyl. An N-6-3-iodobenzyl-3'-ureido adenosine derivative 10 activated phospholipase C in COS-7 cells (EC50 = 0.18 mu M) or phospholipase D in chick primary cardiomyocytes, both mediated by a mutant ( H272E), but not the wild-type, A(3)AR. The affinity enhancements for 10 and the corresponding 3'-acetamidomethyl analogue 6 were > 100-fold and > 20-fold, respectively. 10 concentration-dependently protected cardiomyocytes transfected with the neoceptor against hypoxia. Unlike 10, adenosine activated the wild-type A(3)AR (EC50 of 1.0 mu M), but had no effect on the H272E mutant A(3)AR (100 mu M). Compound 10 was inactive at human A(1), A(2A), and A(2B)ARs. The orthogonal pair comprising an engineered receptor and a modified agonist should be useful for elucidating signaling pathways and could be therapeutically applied to diseases following organ-targeted delivery of the neoceptor gene.

Synthesis of 3'-ureidoadenosines and their high binding affinity at the mutant A3 adenosine receptor
Kim, AY Chung, HO Kim, MJ Chun, MW Lee, KM Jacobson, KA Jeong, LS
Nucleic Acids Res. Suppl. 49 105-106 (2005)

Synthesis of 3 '-ureidoadenosine analogues and their binding affinity to the A(3) adenosine receptor
Chun, MW Lee, HW Kim, AY Kim, MJ Kim, HO Gao, ZG Jacobson, KA Jeong, LS
Nuc. Nuc. Nuc. acids 24 (5-7) 1119-1121 (2005)
<Abstract>

Novel 3'-ureidoadenosine analogues were synthesized from 1,2:5,6-di-O-isopropylidene-D-glucose in order to lead to stronger hydrogen bonding at the A(3) adenosine receptor than the corresponding 3'-aminoadenosine derivatives. However, all synthesized 3'-ureidoadenosine analogues have lost their binding affinities to the all subtypes of adenosine receptors, indicating that bulky 3'-urea moiety led to conformational distortion.

Synthesis of 3 '-deoxy-3 '-C-hydroxym ethyl analogues of tiazofurin and ribavirin
Chun, MW Kim, MJ Shin, JH Jeong, LS
Nuc. Nuc. Nuc. acids 24 (5-7) 975-977 (2005)

Synthesis of homo-N-nucleoside with 1,2,4-triazole-3-carboxamide
Chun, MW Kim, JH Kim, MJ Kim, BR Jeong, LS
Nuc. Nuc. Nuc. acids 24 (5-7) 979-981 (2005)
<Abstract>

On the basis of Potent biological activities of ribavirin and homo-N-nucleosides, a novel homo-N-1,2,4-triazole-3-carboxamide derivative I was synthesized starting from 2,3,5-tri-O-benzoylribofuranosyl- I-acetate as a potential antiviral agent.

Synthesis and biological evaluation of novel isonucleosides with 1,2,4-triazole-3-carboxamide
Kim, MJ Chung, SY Chun, MW
Synth. Commun. 35 (20) 2653-2663 (2005)
<Abstract>

Novel 1,2,4-triazole isonucleosides (1 and 2) were efficiently synthesized starting from D-ribose and D-xylose, respectively. The key steps were condensation of cyclic sulfate 8 with methyl-1,2,4-triazole-3-carboxylate and nucleophilic displacement of the tosylate 15 with methyl-1,2,4-triazole-3-carboxylate, respectively.

Design and synthesis of 3 '-ureidoadenosine-5 '-uronamides: effects of the 3 '-ureido group on binding to the A(3) adenosine receptor
Jeong, LS Kim, MJ Kim, HO Gao, ZG Kim, SK Jacobson, KA Chun, MW
Bioorg. Med. Chem. Lett. 14 (19) 4851-4854 (2004)
<Abstract>

On the basis of high binding affinity at the A(3) adenosine receptor of 3'-aminoadenosine derivatives with hydrogen bonding donor ability, novel 3'-ureidoadenosine analogues were synthesized from 1,2:5,6-di-O-isopropylidene-D-glucose in order to lead to stronger hydrogen bonding than the corresponding 3'-aminoadeno sine derivatives. However, the synthesized 3'-ureidoadenosine analogues were totally devoid of binding affinity, because 3'-urea moiety caused steric and electrostatic repulsions at the binding site of the A(3) adenosine receptor, leading to conformational distortion. (C) 2004 Elsevier Ltd. All rights reserved.

Synthesis and biological evaluation of novel apio nucleosides with thiazole-4-carboxamide and 1,2,4-triazole-3-carboxamide
Kim, MJ Jeong, LS Kim, JH Shin, JH Chung, SY Lee, SK Chun, MW
Nuc. Nuc. Nuc. acids 23 (4) 715-724 (2004)
<Abstract>

In view of biological activities of azole nucleosides and apio-dideoxynucleoside, novel apio nucleoside analogues (1 and 2) with thiazole and triazole base moiety were synthesized using 2,3-O-isopropylidene-apio-beta-D-furanose (3), which was prepared from D-mannose.

Synthesis and biological evaluation of thymine nucleosides fused with 3 ',4 '-tetrahydrofuran ring
Kim, MJ Kim, HO Kim, HD Kim, JH Jeong, LS Chun, MW
Bioorg. Med. Chem. Lett. 13 (20) 3499-3501 (2003)
<Abstract>

The pyrimidine nucleosides fused with 3',4'-tetrahydrofuran ring were successfully synthesized, starting from 1,2;5,6-di-O-isopropylidene-D-glucose and assayed for antiviral activities against HIV-1, HIV-2, EMCV, Cox. B3 and VSV. Thymine analogue (5) and its corresponding 2'-deoxy analogue (6) exhibited high cytotoxicity instead of giving antiviral activities. (C) 2003 Elsevier Ltd. All rights reserved.

Synthesis of 2-(3 '-azido- and 3 '-amino-3 '-deoxy-beta-D-ribofuranosyl)thiazole-4-carboxamide
Liang, CW Kim, MJ Jeong, LS Chun, MW
Nuc. Nuc. Nuc. acids 22 (11) 2039-2048 (2003)
<Abstract>

In view of biological activities of tiazofurin and azido or aminosugar nucleosides, novel azido- and amino-substituted tiazofurin derivatives (I and 2) were efficiently synthesized starting from 1,2;5,6-di-O-isopropylidene-D-glucose.

Synthesis and biological evaluation of pyrimidine nucleosides fused with 3 ',4 '-tetrahydrofuran ring
Chun, MW Kim, MJ Kim, HO Moon, HR Kim, HD Kim, JH Jeong, LS
Nuc. Nuc. Nuc. acids 22 (5-8) 719-721 (2003)
<Abstract>

Pyrimidine nucleosides fused with 3,4'-tetrahydrofuran ring were synthesized, starting from 1,2;5,6-di-O-isopropylidene-D-glucose and assayed for antiviral activities. Thymine analogue 1 and its corresponding 2'-deoxy analogue 3 exhibited high cytotoxicity instead of giving antiviral activities.

Synthesis of 5-azacytidine nucleosides with rigid sugar moiety as potential antitumor agents
Chun, MW Kim, MJ Kim, HO Kim, HD Kim, JH Moon, HR Jeong, LS
Nuc. Nuc. Nuc. acids 22 (5-8) 915-917 (2003)
<Abstract>

The bicyclic 3'-O,5'-C-methylene-linked and 2'-O,5'-C-methylene-linked 5-azacytidine derivatives were readily synthesized from 1,2;5,6-di-O-isopropylidene-D-glucose and evaluated against several cancer cell lines.

Synthesis of novel 3 '-deoxy-3 '-C-hydroxymethyl nucleosides with conformationally rigid sugar moiety as potential antiviral agents
Chun, MW Kim, MJ Jo, UH Kim, JH Kim, HD Jeong, LS
Nuc. Nuc. Nuc. acids 20 (4-7) 699-702 (2001)
<Abstract>

Based on the fact that the ring expanded 3'-C-hydroxymethyl analogue of oxetanocin A exhibited potent antiviral activity, two types of conformationally rigid 3'-C-hydroxymethyl derivatives in which 2'-hydroxyl group is linked to the 4'-position or to the 6'-position were synthesized starting from 1,2;5,6-di-O-isopropylidene-D-glucose, respectively.

Synthesis of novel D- and L-3 '-deoxy-3 '-C-hydroxymethyl nucleoside with exocyclic methylene as potential ribonucleotide reductase inhibitor
Chun, MW Kim, MJ Jo, UH Kim, JH Kim, HD Jeong, LS
Nuc. Nuc. Nuc. acids 20 (4-7) 703-706 (2001)
<Abstract>

D- and L-3'-Deoxy-3'-C-hydroxymethyl thymidine substituted with exocyclic methylene at 2'-position were synthesized, starting from D- and L-xylose as potential ribonucleotide reductase inhibitor, respectively, but they were found to be inactive against several tumor cell lines.

Synthesis and antiviral activities of 1,3-oxathiolanyl nucleosides with 5-hydroxymethyl substituent
Chun, MW Choi, SP Kim, MJ Bae, CJ
Nucl. Nucl. 18 (4-5) 615-616 (1999)
<Abstract>

Novel 1,3-oxathiolanyl pyrimidine nucleosides with 5-hydroxymethyl substituent were synthesized starting from D-mannose and evaluated for antiviral activities against HIV-1, HSV type 1,2 and HCMV.