Interaction between nucleic acids and glycans: In silico and in vitro

Quantum-chemical (PM3) calculations prove the possibility of hydrogen bonding between all nucleic bases and carboxyls of acidic or hydroxymethyls of neutral sugars, with energy in the former case comparable to that for canonical GC or AT pairing. However, there is appreciable energy preference for carboxyl H-bonding with purines, and for hydroxymethyl H-bonding with pyrimidines. Simulation reveals that the H-bonds formed in purine-uronide and pyrimidine-hexose pairs can give rise to double-stranded nucleic acid-polysaccharide complexes. Indeed, dot hybridization with radioactive probes and hypochromic effects in solution testify that a hexose homoglycan (amylose) selectively forms a complex with polypyrimidine, whereas uronic acid homoglycans selectively complex with polypurine. Complexing is also observed between heteropolymers such as thymus DNA and hyaluronic acid. These results are consistent with the idea of template-directed synthesis of the polysaccharide moiety of glycosaminoglycans involving nucleic acids.