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1.  (α,α-dimethyl)glycyl (dmg) PNAs 
Artificial DNA, PNA & XNA  2012;3(1):5-13.
The design and facile synthesis of sterically constrained new analogs of PNA having gem-dimethyl substitutions on glycine (dmg-PNA-T) is presented. The PNA oligomers [aminoethyl dimethylglycyl (aedmg) and aminopropyl dimethylglycyl (apdmg)] synthesized from the monomers 6 and 12) effected remarkable stabilization of homothyminePNA2:homoadenine DNA/RNA triplexes and mixed base sequence duplexes with target cDNA or RNA. They show a higher binding to DNA relative to that with isosequential RNA. This may be a structural consequence of the sterically rigid gem-dimethyl group, imposing a pre-organized conformation favorable for complex formation with cDNA. The results complement our previous work that had demonstrated that cyclohexanyl-PNAs favor binding with cRNA compared with cDNA and imply that the biophysical and structural properties of PNAs can be directed by introduction of the right rigidity in PNA backbone devoid of chirality. This approach of tweaking selectivity in binding of PNA constructs by installing gem-dimethyl substitution in PNA backbone can be extended to further fine-tuning by similar substitution in the aminoethyl segment as well either individually or in conjunction with present substitution.
PMCID: PMC3368815  PMID: 22679528
(α,α-dimethyl)glycyl PNA; gem-dimethylglycyl PNA; peptide nucleic acid; PNA-DNA binding; sterically constrained PNA analog; α-aminoisobutyric acid PNA
2.  1,4-linked 1,2,3-Triazole des-peptidic analogues of PNA (TzNA) 
Artificial DNA, PNA & XNA  2010;1(2):68-75.
1,2,3-triazole analogues of PNA (TzNA) in which the amide link in backbone is replaced by triazole ring is synthesized on solid phase by ‘click’ chemistry and such triazolothymine PNA chimeric oligomers are shown to significantly stabilize the derived PNA2:DNA triplexes. With increasing number of triazole units in the backbone, single stranded PNA oligomers exhibit enhanced self-ordering.
PMCID: PMC3116575  PMID: 21686241
PNA analogues; solid phase click chemistry; triazolyl oligimers; XNA; chimeric PNA-XNA; triazole PNA
3.  HIV-1 Tat directly binds to NFκB enhancer sequence: role in viral and cellular gene expression 
Nucleic Acids Research  2004;32(4):1270-1278.
HIV-1 Tat protein reprograms cellular gene expression of infected as well as uninfected cells apart from its primary function of transactivating HIV-1 long terminal repeat (LTR) promoter by binding to a nascent RNA stem–loop structure known as the transactivator response region (TAR). Tat also induces chromatin remodeling of proviral LTR-mediated gene expression by recruiting histone acetyl transferases to the chromatin, which results in histone acetylation. Furthermore several studies have shown convincing evidence that Tat can transactivate HIV-1 gene expression in the absence of TAR, the molecular mechanism of which remains to be elucidated. Here we show a direct interaction of Tat with nuclear factor kappa B (NFκB) enhancer, a global regulatory sequence for many cellular genes both in vitro and in vivo. This interaction not only provides a novel molecular basis to explain TAR-independent transactivation in HIV-1, but also points toward the potential mechanism of Tat- mediated modulation of cellular genes.
PMCID: PMC390279  PMID: 14981150
4.  Recognition of 5-aminouracil (U#) in the central strand of a DNA triplex: orientation selective binding of different third strand bases 
Nucleic Acids Research  2000;28(5):1162-1169.
A necessary feature of the natural base triads for triplex formation is the requirement of a purine (A or G) in the central position, since only these provide sets of two hydrogen bond donors/acceptors in the major groove of the double helix. Pyrimidine bases devoid of this feature have incompatible complementarity and lead to triplexes with lower stability. This paper demonstrates that 5-aminouracil (U#) (I), a pyrimidine nucleobase analogue of T in which 5-methyl is replaced by 5-amino group, with hydrogen bonding sites on both sides, is compatible in the central position of triplex triad X*U#·A, where X = A/G/C/T/2-aminopurine (AP), and * and · represent Hoogsteen and Watson–Crick hydrogen bonding patterns respectively. A novel recognition selectivity based on the orientation (parallel/antiparallel) of the third strand purines A, G or AP with A in the parallel motif (Ap*U#·A), and G/AP in the antiparallel motif (Gap/APap*U#·A) is observed. Similarly for pyrimidines in the third strand, C is accepted only in a parallel mode (Cp*U#·A). Significantly, T is recognised in both parallel and antiparallel modes (Tp/Tap*U#·A), with the antiparallel mode being stable compared to the parallel one. The ‘U#’ triplexes are also more stable than the corresponding control ‘T’ triplexes. The results expand the lexicon of triplex triads with a recognition motif consisting of pyrimidine in the central strand.
PMCID: PMC102601  PMID: 10666458

Results 1-4 (4)