Associate
Myong-Jung Kim

Education

BS in Pharmacy. Seoul National University, Korea (1997)
MS in Medicinal Chemistry. Seoul National University, Korea (1999)
PhD in Medicinal Chemistry. Seoul National University, Korea (2002)

Research summary

My research focuses on the design and synthesis of a periodate-cleavable linker and 3'-O-modified fluorescent reversible nucleotide terminators for DNA sequencing by synthesis.

Recent Publications

Labeled nucleoside triphosphates with reversibly terminating aminoalkoxyl groups
Hutter, D; Kim, MJ; Karalkar, N; Leal, NA; Chen, F; Guggenheim, E; Visalakshi, V; Olejnik, J; Gordon, S; Benner, SA
Nuc. Nuc. Nuc. acids 29 (11) 879-895 (2010)
<Abstract>

Nucleoside triphosphates having a 3'-ONH(2) blocking group have been prepared with and without fluorescent tags on their nucleobases. DNA polymerases were identified that accepted these, adding a single nucleotide to the 3'-end of a primer in a template-directed extension reaction that then stops. Nitrite chemistry was developed to cleave the 3'-ONH(2) group under mild conditions to allow continued primer extension. Extension-cleavage-extension cycles in solution were demonstrated with untagged nucleotides and mixtures of tagged and untagged nucleotides. Multiple extension-cleavage-extension cycles were demonstrated on an Intelligent Bio-Systems Sequencer, showing the potential of the 3'-ONH(2) blocking group in "next generation sequencing."

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 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 24 975-977 (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 24 979-981 (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.

(View all publications by Myong-Jung Kim)

Associate
Myong-Jung Kim

Education

Research summary

Recent Publications

Interests

Contact

Associate Myong-Jung Kim

Education

Research summary

Recent Publications

Interests

Contact

Associate
Myong-Jung Kim