Cationic porphyrins are known to bind to and stabilize different types of G-quadruplexes. Recent studies have shown the biological relevance of the intramolecular parallel G-quadruplex as a transcriptional silencer in the c-MYC promoter. TMPyP4 also binds to this G-quadruplex and most likely converts it to a mixed parallel/antiparallel G-quadruplex with two external lateral loops and one internal propeller loop, suppressing c-MYC transcriptional activation. To achieve therapeutic selectivity by targeting G-quadruplexes, it is necessary to synthesize drugs that can differentiate among the different types of G-quadruplexes. We have designed and synthesized a core-modified expanded porphyrin analogue, 5,10,15,20-[tetra(N-methyl3-pyridyl)]-26,28-diselenasapphyrin chloride (Se2SAP). Se2SAP converts the parallel c-MYC G-quadruplex into a mixed parallel/antiparallel G-quadruplex with one external lateral loop and two internal propeller loops, resulting in strong and selective binding to this G-quadruplex. A Taq polymerase stop assay was used to evaluate the binding of TMPyP4 and Se2SAP to G-quadruplex DNA. Compared to TMPyP4, Se2SAP shows a greater selectivity for and a 40-fold increase in stabilization of the single lateral-loop hybrid. Surface plasmon resonance and competition experiments with duplex DNA and other G-quadruplexes further confirmed the selectivity of Se2SAP for the c-MYC G-quadruplex. Significantly, Se2SAP was found to be less photoactive and noncytotoxic in comparison to TMPyP4. From this study, we have identified an expanded porphyrin that selectively binds with the c-MYC G-quadruplex in the presence of duplex DNA and other G-quadruplexes.
机构:
Univ Toronto, Leslie Dan Fac Pharm, Dept Pharmaceut Sci, Toronto, ON M5S 3M2, CanadaUniv Toronto, Leslie Dan Fac Pharm, Dept Pharmaceut Sci, Toronto, ON M5S 3M2, Canada
Kim, Byul G.
Evans, Heather M.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Toronto, Leslie Dan Fac Pharm, Dept Pharmaceut Sci, Toronto, ON M5S 3M2, CanadaUniv Toronto, Leslie Dan Fac Pharm, Dept Pharmaceut Sci, Toronto, ON M5S 3M2, Canada
Evans, Heather M.
Dubins, David N.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Toronto, Leslie Dan Fac Pharm, Dept Pharmaceut Sci, Toronto, ON M5S 3M2, CanadaUniv Toronto, Leslie Dan Fac Pharm, Dept Pharmaceut Sci, Toronto, ON M5S 3M2, Canada
Dubins, David N.
Chalikian, Tigran V.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Toronto, Leslie Dan Fac Pharm, Dept Pharmaceut Sci, Toronto, ON M5S 3M2, CanadaUniv Toronto, Leslie Dan Fac Pharm, Dept Pharmaceut Sci, Toronto, ON M5S 3M2, Canada
机构:
Univ Arizona, Coll Pharm, Tucson, AZ 85721 USAUniv Arizona, Coll Pharm, Tucson, AZ 85721 USA
Boddupally, Peda V. L.
Hahn, Seongmin
论文数: 0引用数: 0
h-index: 0
机构:
Univ Arizona, Coll Pharm, Tucson, AZ 85721 USAUniv Arizona, Coll Pharm, Tucson, AZ 85721 USA
Hahn, Seongmin
Beman, Cristina
论文数: 0引用数: 0
h-index: 0
机构:
Univ Arizona, Coll Pharm, Tucson, AZ 85721 USAUniv Arizona, Coll Pharm, Tucson, AZ 85721 USA
Beman, Cristina
De, Biswanath
论文数: 0引用数: 0
h-index: 0
机构:
Univ Arizona, Coll Pharm, Tucson, AZ 85721 USAUniv Arizona, Coll Pharm, Tucson, AZ 85721 USA
De, Biswanath
Brooks, Tracy A.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Arizona, Coll Pharm, Tucson, AZ 85721 USA
Univ Arizona, BIOS Inst, Tucson, AZ 85721 USA
Univ Arizona, Arizona Canc Ctr, Tucson, AZ 85724 USAUniv Arizona, Coll Pharm, Tucson, AZ 85721 USA
Brooks, Tracy A.
Gokhale, Vijay
论文数: 0引用数: 0
h-index: 0
机构:
Univ Arizona, Coll Pharm, Tucson, AZ 85721 USA
Univ Arizona, BIOS Inst, Tucson, AZ 85721 USA
Univ Arizona, Arizona Canc Ctr, Tucson, AZ 85724 USAUniv Arizona, Coll Pharm, Tucson, AZ 85721 USA
Gokhale, Vijay
Hurley, Laurence H.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Arizona, Coll Pharm, Tucson, AZ 85721 USA
Univ Arizona, BIOS Inst, Tucson, AZ 85721 USA
Univ Arizona, Arizona Canc Ctr, Tucson, AZ 85724 USAUniv Arizona, Coll Pharm, Tucson, AZ 85721 USA
机构:
Zhejiang Univ Technol, Inst Drug Dev & Chem Biol, Hangzhou 310014, Peoples R ChinaZhejiang Univ Technol, Inst Drug Dev & Chem Biol, Hangzhou 310014, Peoples R China
Jiang, Shikun
Awadasseid, Annoor
论文数: 0引用数: 0
h-index: 0
机构:
Zhejiang Univ Technol, Inst Drug Dev & Chem Biol, Hangzhou 310014, Peoples R ChinaZhejiang Univ Technol, Inst Drug Dev & Chem Biol, Hangzhou 310014, Peoples R China
Awadasseid, Annoor
论文数: 引用数:
h-index:
机构:
Narva, Suresh
Cao, Song
论文数: 0引用数: 0
h-index: 0
机构:
East China Univ Sci & Technol, Coll Pharm, Shanghai 021, Peoples R ChinaZhejiang Univ Technol, Inst Drug Dev & Chem Biol, Hangzhou 310014, Peoples R China
Cao, Song
Tanaka, Yoshimasa
论文数: 0引用数: 0
h-index: 0
机构:
Kyoto Univ, Ctr Innovat Immunoregulat Technol & Therapeut, Grad Sch Med, Kyoto 6068501, JapanZhejiang Univ Technol, Inst Drug Dev & Chem Biol, Hangzhou 310014, Peoples R China
Tanaka, Yoshimasa
Wu, Yanling
论文数: 0引用数: 0
h-index: 0
机构:
Zhejiang Prov Ctr Dis Control & Prevent, Lab Mol Immunol, Virus Inspect Dept, Hangzhou 310051, Peoples R ChinaZhejiang Univ Technol, Inst Drug Dev & Chem Biol, Hangzhou 310014, Peoples R China
Wu, Yanling
Fu, Wei
论文数: 0引用数: 0
h-index: 0
机构:
Zhejiang Univ Technol, Inst Drug Dev & Chem Biol, Hangzhou 310014, Peoples R ChinaZhejiang Univ Technol, Inst Drug Dev & Chem Biol, Hangzhou 310014, Peoples R China
Fu, Wei
Zhao, Xiaoyin
论文数: 0引用数: 0
h-index: 0
机构:
Zhejiang Univ Technol, Inst Drug Dev & Chem Biol, Hangzhou 310014, Peoples R ChinaZhejiang Univ Technol, Inst Drug Dev & Chem Biol, Hangzhou 310014, Peoples R China
Zhao, Xiaoyin
Wei, Chuanhe
论文数: 0引用数: 0
h-index: 0
机构:
Zhejiang Univ Technol, Inst Drug Dev & Chem Biol, Hangzhou 310014, Peoples R ChinaZhejiang Univ Technol, Inst Drug Dev & Chem Biol, Hangzhou 310014, Peoples R China
Wei, Chuanhe
Zhang, Wen
论文数: 0引用数: 0
h-index: 0
机构:
Zhejiang Univ Technol, Inst Drug Dev & Chem Biol, Hangzhou 310014, Peoples R ChinaZhejiang Univ Technol, Inst Drug Dev & Chem Biol, Hangzhou 310014, Peoples R China
机构:
Hong Kong Baptist Univ, Dept Chem, Kowloon Tong, Hong Kong, Peoples R ChinaHong Kong Baptist Univ, Dept Chem, Kowloon Tong, Hong Kong, Peoples R China
Yang, H.
Ma, V. P. -Y.
论文数: 0引用数: 0
h-index: 0
机构:
Hong Kong Baptist Univ, Dept Chem, Kowloon Tong, Hong Kong, Peoples R ChinaHong Kong Baptist Univ, Dept Chem, Kowloon Tong, Hong Kong, Peoples R China
Ma, V. P. -Y.
Chan, D. S. -H.
论文数: 0引用数: 0
h-index: 0
机构:
Hong Kong Baptist Univ, Dept Chem, Kowloon Tong, Hong Kong, Peoples R ChinaHong Kong Baptist Univ, Dept Chem, Kowloon Tong, Hong Kong, Peoples R China
Chan, D. S. -H.
He, H. -Z.
论文数: 0引用数: 0
h-index: 0
机构:
Hong Kong Baptist Univ, Dept Chem, Kowloon Tong, Hong Kong, Peoples R ChinaHong Kong Baptist Univ, Dept Chem, Kowloon Tong, Hong Kong, Peoples R China
He, H. -Z.
Leung, C. -H.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Taipa, Peoples R ChinaHong Kong Baptist Univ, Dept Chem, Kowloon Tong, Hong Kong, Peoples R China
Leung, C. -H.
Ma, D. -L.
论文数: 0引用数: 0
h-index: 0
机构:
Hong Kong Baptist Univ, Dept Chem, Kowloon Tong, Hong Kong, Peoples R ChinaHong Kong Baptist Univ, Dept Chem, Kowloon Tong, Hong Kong, Peoples R China