Binding of uracil derivatives to hydrophobic peptides and sodium dodecyl sulfate

The capacities of five hydrophobic peptides to bind 13 alkyl uracil derivatives have been assessed as a first step toward constructing polymeric molecules, related to the nucleic acids, that specifically complement protein molecules. The peptides were Phe-Phe-Phe-Glu-Glu and its structural analogs with leucine, isoleucine, methionine, and valine substituted for phenylalanine. Uracils with the following substituents in position 5' were used: i-propyl, i-butyl, i-pentyl, sec-butyl, n-butyl, phenyl, benzyl, phenylethyl, methylthioethyl, ethylthiomethyl, and ethylthioethyl. 6-Benzyl and 6-i-pentyl uracils were also tested. The variations in base binding patterns are unique for each peptide, and the general effectiveness of the peptides in binding is related to the order in which their hydrophobic amino acid constituents occur in the uracil column of the genetic codon table. Although the method used does not permit precise determination of binding constants, it is apparent that many of them are much lower than 1 mM. 5-Ethylthioethyluracil quite selectively forms a large metastable aggregate with Phe3Glu2. Its close homologues do not. Also, 5-ethylthioethyluracil binds in some measure to Met3Glu2 but not significantly to Ile3Glu2 and Val3Glu2, whereas its homologue, 5-ethylthiomethyluracil, binds better to the latter two than to Met3Glu2. Thus, the two homologues might serve to form hypothetical polymers that discriminatively bind polymers of isoleucine and valine. It is argued that evolution would most reasonably have begun with such crude mechanisms.