Cyanamide mediated syntheses of peptides containing histidine and hydrophobic amino acids.

Abstract

Using the model of a primitive earth evaporation pond, the synthesis of three histidyl peptides in yields up to 11% was demonstrated when aqueous solutions of histidine, leucine, ATP, cyanamide, and MgCl2 were evaporated and heated for 24 h at 80 degrees C. In addition, peptides were formed in yields of up to 56%, 35%, and 21%, respectively for phenylalanine, leucine, and alanine when aqueous solutions of the appropriate amino acid were evaporated and heated with cyanamide and one or more of the following components: ATP, AMP, 4-amino-5-imidazole carboxamide, or MgCl2. The greatest peptide yield occurred at pH 3. But peptide formation was demonstrated for a system of Leu, cyanamide, and MgCl2 adjusted to pH 7 with NH4OH. Peptide synthesis was also studied in the presence of CaCl2, ZnCl2, different adenosine nucleotides, and UTP to compare their effects on peptide synthesis. The optimum conditions for cyanamide mediated peptide synthesis were also studied in terms of pH, reaction time, reaction temperature, and cyanamide concentration. The major side product in nearly all reactions studied appears to be an amino acid-cyanamide adduct. Peptides were analyzed and identified by thin layer chromatography, acid hydrolysis, and enzymatic degradation.