R. Lohrmann

Urea-inorganic phosphate mixtures as prebiotic phosphorylating agents.

Previous attempts to phosphorylate nucleosides by heating with inorganic phosphate succeeeded only when acid phosphates such as Ca(HPO4)2 were used. The addition of urea and ammonium chloride to the reaction mixture permits phosphorylation in high yield with neutral or basic phosphates at temperatures in the range of 65� to 100�C. Since the abundant mineral, hydroxylapatite, is a satisfactory substrate for this reaction, we believe that this procedure plausible model for prebiotic phosphorylation.

Catalysts for the self-polymerization of adenosine cyclic 2′,3′-phosphate

SummaryWhen adenosine cyclic 2′,3′-phosphate is evaporated from solution in the presence of simple catalysts such as aliphatic diamines at alkaline pH, and maintained in a dry state at moderate temperatures (25-85°C), self-polymerization to give oligonucleotides of chainlength up to at least 6 is observed. The products contain an excess of [3′→5′]-linkages over [2′→5′]-linkages. The effects of different catalysts and reaction conditions on the efficiency of the reaction are described. The prebiological relevance of these reactions is discussed.

Catalysts for the polymerization of adenosine cyclic 2′,3′-phosphate on a poly (U) template

Abstract A number of polybasic amines and glycine derivatives stabilize the triple helix formed by adenosine cyclic 2′,3′-phosphate with poly (U). Many of these compounds also catalyze the formation of dinucleoside diphosphates from adenosine cyclic 2′,3′-phosphate and so may be considered as simple models for prebiotic catalysts.

Formation of nucleoside 5′-phosphoramidates under potentially prebiological conditions

SummaryAdenosine 5′-phosphoramidates form when solutions containing adenosine 5′-polyphosphates pnA (n ≧ 3) or P1, P2-diadenosine 5′-diphosphate and amines are allowed to dry out. Mg ions catalyze these reactions. We have studied systems containing ammonia, imidazole, glycine, ethylenediamine and histamine. The yields of adenosine 5′-phosphoramidates range from 10–50 % based on the nucleotide. The prebiotic significance of the reactions is discussed.

Further studies of urea-catalyzed phosphorylation reactions

SummaryWe have analyzed the products formed when mixtures of a nucleoside and ammonium dihydrogen phosphate are heated with an excess of urea. If there is more phosphate than nucleoside in the mixture, compounds containing pyrophosphate bonds are obtained. If uridine, as nucleoside, is in excess over phosphate, di- and oligonucleotides are formed.

Template-directed synthesis and selective adsorption of oligoadenylates on hydroxyapatite

SummaryPolyuridylic acid is adsorbed completely from aqueous solution by hydroxyapatite under conditions that permit template-directed synthesis of oligoadenylates in free solution. The yield of oligoadenylates is enhanced to almost the same extent by poly(U) in the presence or the absence of hydroxyapatite. Under very similar conditions small quantities of hydroxyapatite adsorb higher molecular-weight oligoadenylates selectively from a mixture of oligomers.On the basis of these results we propose a mechanism for prebiotic oligonucleotide formation in which selective adsorption on hydroxyapatite or some other immobilized anion-exchanging material plays a major role. Monomers are released from the surface for reactivation, while oligomers are retained in a protected environment by adsorption to the apatite surface.

The mechanism of the trimetaphosphate-induced peptide synthesis

Abstract The formation of peptides from glycine in the presence of trimetaphosphate proceeds mainly via peptide-N-phosphates as intermediates. The interaction of glycine with trimetaphosphate leads first to the formation of a cyclic acylphosphoamidate and pyrophosphate. The cyclic compound then reacts with the free amine group of glycine or diglycine to give diglycine-N-phosphate or triglycine-N-phosphate.

Prebiotic peptide-formation in the solid state. I. Reactions of benzoate ion and glycine with adenosine 5'-phosphorimidazolide.

SummaryThe reactions of benzoate ion and of glycine with adenosine 5′-phosphorimidazolide have been investigated. Benzoate reacts first to give the anhydride, benzoyl-adenylate, which, in the presence of excess imidazole, reacts further to give the 2′- and 3′-esters of adenosine 5′-phosphate. Glycine also first attacks the imidazolide to give an anhydride, but this compound may react further either to give 2′- and 3′-esters or to form peptides, depending on the reaction conditions.

Template-directed synthesis of high molecular weight polynucleotide analogues.

A GREAT deal is known about the structures of nucleic acids and the mechanisms involved in nucleic acid replication. This relatively new knowledge has led a number of authors to speculate that other linear heteropolymers might be able to serve as carriers of genetic information. A number of polynucleotide analogues have been synthesised by chemical or enzymatic methods1–7 and one of them has been used as a template for RNA polymerase4. Two studies, in particular, have some relationship to the present work. 3′–5′-Linked polynucleotides derived from 2′-amino-2′-deoxynucleoside 5′-phosphates have been synthesised enzymatically7. Letsinger et al.5,6 reported the chemical and enzymatic formation of polydeoxyribonucleotides containing N5′–O3′-phosphoramidate linkages. Here we discuss nucleic acid analogues derived from 2′-amino-2′-deoxynucleotides that we believe may be capable of non-enzymatic replication, and describe some experimental results which, although they are far from establishing the principle of self-replication, do show that it is possible to synthesise fairly long oligomers on templates in aqueous solution.

Template-directed synthesis of oligoadenylates catalyzed by Pb2+ ions.

SummaryThe Pb2+ ion is an effective catalyst for the template-directed condensation of ImpA on poly(U). This reaction generates up to 35% of oligomers 5 or more units long. Furthermore, the product is predominantly 3′–5′-linked (75%) unlike that from the uncatalyzed reaction which is more than 90% 2′–5′-linked. The significance of metal-ion catalysis for prebiotic polynucleotide formation is discussed.