Hydrogen bonding between cytosine and peptides of threonine or serine: Is it relevant to the origin of the genetic code?

Abstract

13C, 15N, and 1H nuclear magnetic resonance measurements indicate that chloroform-soluble threonine-containing tripeptide derivatives, such as t-Boc-Thr-Gly-Gly-OBz, form three strong hydrogen bonds to the cytosine moiety of 2′,3′-O-isopropylidene-5′-O-t-butyldimethylsilylcytidine. The CO and NH of the central peptide residue plus the OH of the threonine side chain appear to form bonds to the N(4′)H 2, N(3), and C(2)O, respectively, of the pyrimidine. An association constant calculated from the cytidine 15N(4′) nuclear magnetic resonance response to added peptide is four times larger than the corresponding cytosine-guanine constant. It is suggested that cytosinepeptide bonding was part of the primitive genetic coding mechanism early in evolution and accounts for the origin of the cytosine-centered codons for the hydroxy amino acids, serine and threonine, in the present code.