O-methyl (3′-6) and (5′-6) thymidinyl gluco-and mannopyranosides and (3′-6) thymidinyl glucofuranose can be synthesised in excellent yields by applying the phosphotriester method. The lipophilic phosphotriesters thus obtained are designed as carriers of nucleoside drugs across cellular membranes.

Different ‘thiophilicity’ of water-soluble carbodiimides to sulfhydryl anions in mono-and diesters of phosphorothioic acid was demonstrated. The EDC (l-ethyl-3-(3-dimethylaminopropyl)carbodiimide) treatment of oligonucleotides containing phosphorothioate diesters with non-bridging sulfur leads to formation of stable adducts which can be isolated by PAGE or HPLC. In contrast, oligomers with terminal phosphorothioate monoesters form with EDC highly reactive intermediates which react easily with media nucleophiles (e.g. water or methanol, phosphomonoester anions).

A series of 2′,3′-dideoxy-2′-fluoro-L-threo-pentofuranosyl nucleosides has been synthesized as potential antiviral agents. The synthesized compounds were evaluated against HIV-1, HBV, HSV-1, and HSV-2. Among the synthesized analogues, only the cytosine derivative showed moderate antiviral activity against HIV and HBV.

A uridine-based linker immobilized onto polystyrene beads at the 5′ terminus via a phosphodiester group and then used as a universal DNA synthesis support gives post synthesis DNA cleavage in 8 hrs or less without alkali metal salts. DNA produced with the new support was analyzed by HPLC, MALDI mass spectroscopy and PAGE. Each analysis showed DNA of equivalent quality to that produced with standard CPG supports, without contaminating materials resulting from linker or support backbone decomposition.

Improved methods of preparing 2′-deoxyribonucleoside and ribonucleoside 3′-phosphoramidites with allylic protecting groups, which serve as useful building blocks, particularly for the synthesis of base-labile derivatives, are developed.

A strong and specific stabilization of a DNA undecamer containing an analog of the abasic site has been induced by the macrocyclic Bisacridine 1 . 1H NMR analysis and molecular modeling of the structure of the complex showed that the drug was specifically docked into the apurinic pocket.

A 2-sperminoguanosine nucleotide has been synthesized and incorporated into oligonucleotides which showed increased duplex melting termperature.

Trinucleotide phosphoramidites that correspond to the codons of all 20 amino acids were synthesized in high yield in 5g scale. Precursors of those amidites - trinucleotide phosphotriesters - have been prepared using the phosphotriester approach without protection of the 3′-hydroxyl function. More than 10 oligonucleotides up to 90 bases long have been synthesized by a phosphite-triester approach using new synthons. The 67-mer (12 random codons) has been used to generate a display library of 2 × 108 complexity.

In recent times, PNA (I), a structural mimic of DNA in which the sugar-phosphate backbone is replaced by N-(2-aminoethyl)glycine (aeg) linkage has emerged as a potential antisense therapeutic agent.1 A major limitation of PNAs from an application perspective is their poor solubility in aqueous medium and being achiral, they bind to cDNA in both parallel (N-PNA/5′-DNA) and antiparallel (N-PNA/3′-DNA) modes. In this connection, we have designed spermine conjugated and conformationally constrained PNA analogues to generate the 4-aminoprolyl backbone (II).2 These were synthesised and evaluated for their DNA binding abilities by using UV and CD spectroscopic studies. It is seen that incorporation of one 4-aminoprolyl unit at the N-terminus of a PNA chain not only enhances the inherent binding of PNA to DNA, but also imparts significant bias in parallel and antiparallel binding with cDNA. Conjugation of spermine at C-terminus enhanced the PNA solubility.

Oligopeptides containing Nβ-(thymin-1-ylacetyl) β-aminoalanine and Nβ-(cytosin-1-ylacetyl) β-aminoalanine moieties synthesized on solid phase using standard boc-chemistry showed hybridization properties with single stranded DNA and RNA, and also with double stranded DNA at pH 7.0.