The effects of thioketo substitution upon uracil-adenine interactions in polyribonucleotides. Synthesis and properties of poly (2-thiouridylic acid) and poly(2,4-dithiouridylic acid).

Abstract

The physical and biological properties of two new poly(U) analogs, poly(2‐thiouridylic acid) or poly(s2U) and poly(2,4‐dithiouridylic acid) or poly(s2s4U) have been investigated. Ultraviolet absorption and circular dichroism spectra of poly(s2U) and poly(s2s4U) as well as those of the corresponding monomers were measured. Absorption‐temperature and absorption‐pH profiles of both poly(s2U) and poly(s2s4U) displayed sharp cooperative transitions. The phase transition diagrams of poly(s2U) and poly(s2s4U) show the high stability of their secondary structures. Neither poly(s2U) nor poly(s2s4U) formed helical complexes with poly(A). It was concluded from the corresponding phase transition diagrams that the reason for this behaviour is the larger thermodynamical stability of the poly(s2U) or poly(s2s4U) helices over the hypothetical complexes poly(s2U) · poly(A) or poly(s2s4U) – poly(A). Sedimentation velocity analysis of poly(s2U) and poly(s2s4U) revealed sedimentation coefficients S20,w of 28 S and 12 S, respectively. A more detailed analysis of poly(s2U) lead to the conclusion that poly(s2U) exists as an intra‐molecular associate of two anti‐parallel poly(s2U) strands in the form of a large hairpin. Consistent with their physical properties, poly(s2U) and poly(s2s4U) are not able to replace poly(U) as messengers in the cell‐free synthesis of poly(phenylalanine). Poly(s2U) is only poorly, poly(s2s4U) not at all phosphorolyzed by polynucleotide phosphorylase.