Poly(U)-directed peptide-bond formation from the 2'(3')-glycyl esters of adenosine derivatives

Abstract

The self-condensation of 2'(3')-O-glycyl esters of adenosine, adenosine-5'-(O-methylphosphate) and P1, P2-diadenosine-5'-pyrophosphate in 6.2 mM solutions at pH 8.0 and -5 degrees C in the presence of 12.5 mM poly(U) yields approximately 3 times as much diketopiperazine as reactions without poly(U). As the concentration of 2'(3')-O-(glycyl)-P1, P2-diadenosine-5'-pyrophosphate is decreased from 6.2 mM to 1.5 mM the yield of diketopiperazine in the presence of poly(U) decreases slightly from 6.6% to 5.2%, whereas, in the absence of poly(U) the yield of diketopiperazine decreases substantially from 2.4% to 0.75%. The enhanced yield of diketopiperazine that is attributed to the template action of poly(U) is temperature dependent and is observed only at temperatures below 10 degrees C (5 degrees C to -5 degrees C) for 6.2 mM 2'(3')-O-(glycyl)-adenosine-5'-(O-methylphosphate) and below 23 degrees C (15 degrees C to -5 degrees C) for 6.2 mM 2'(3')-O-(glycyl)-P1, P2-diadenosine-5'-pyrophosphate. The absence of a template effect at high temperatures is attributed to the melting of the organized helices. The hydrolysis half-lives at pH 8.0 and -5 degrees C of 2'(3')-O-(glycyl)-adenosine, 2'(3')-O-(glycyl)-adenosine-5'-(O-methylphosphate), 2'(3')-O-(glycyl)-P1, P2-diadenosine-5'-pyrophosphate, and 5'-O-(glycyl)-adenosine in the presence of poly(U) are substantially larger than their half-lives in the absence of poly(U). The condensation of 2'(3')-O-(glycyl)-adenosine yields 5% of 5'-O-(glycyl)-adenosine in the presence of poly(U) compared to 0.7% in the absence of poly(U).