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Nonbonded bivalence approach to cell-permeable molecules that target DNA sequences
- Source :
-
Bioorganic & Medicinal Chemistry . Jun2004, Vol. 12 Issue 11, p3063-3068. 6p. - Publication Year :
- 2004
-
Abstract
- Polyamides such as the natural antibiotic distamycin A can form binary or ternary complexes with B-DNA. The driving forces and advantages for forming the ternary complexes are not fully understood. The computational studies reported herein suggest that three- and four-ring polyamides have a propensity for forming the same dimer conformations in water as those in their ternary complexes. The pre-dimerization of a polyamide in water facilitates the formation of the ternary complex, making the polyamide more selective, and tighter binding to the minor groove whose minimal width is predetermined by the B-DNA sequence. Relative to the dimer tethered with covalent bonds, the smaller, monomeric polyamide available from reversible dimerization in water makes the molecule inherently more cell permeable. A nonbonded bivalence approach that dimerizes molecules by intermolecular interactions is proposed for improving affinity, selectivity, and cell permeability. [Copyright &y& Elsevier]
- Subjects :
- *POLYMERS
*NUCLEOTIDE sequence
*ANTI-infective agents
*POLYAMIDES
Subjects
Details
- Language :
- English
- ISSN :
- 09680896
- Volume :
- 12
- Issue :
- 11
- Database :
- Academic Search Index
- Journal :
- Bioorganic & Medicinal Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 13106510
- Full Text :
- https://doi.org/10.1016/j.bmc.2004.02.026