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Schwartz, Alan W.

Publications and source records attributed to Schwartz, Alan W..

Is ligation the only solution to the pyrophosphate problem?

Pyrophosphate linkages are easily formed during the nonenzymatic oligomerization of activated nucleotides. They often form `caps' which terminate an oligonucleotide with a 5'-5' pyrophosphate. Owing to their structural resemblance to the intermediates in enzymatic ligation reactions, it has been suggested that pyrophosphate caps might have been capable of acting as activating groups in chain elongation processes. We argue that an alternative possibility would have been the specific hydrolysis of pyrophosphates.

Visscher, J.↗

Oligomerizations of deoxyadenosine bis-phosphates and of their 3-prime-5-prime, 3-prime-3-prime, and 5-prime-5-prime dimers - Effects of a pyrophosphate-linked, poly(T) analog

The effect of a 3-prime-5-prime pyrophosphate-linked oligomer of pTp on oligomerizations of pdAp and of its 3-prime-5-prime, 3-prime-3-prime, and 5-prime-5-prime dimers was investigated, using HPLC to separate the reaction mixtures; peak detection was by absorbance monitoring at 254 nm. It was expected that the dimers would form stable complexes with the template, with the degree of stability depending upon the internal linkage of each dimer. It was found that, although the isomers differ substantially in their oligomerization behavior in the absence of template, the analog-template catalyzes the oligomerization to about the same extent in all three cases.

Visscher, J.↗

Was adenine the first purine?

Oligomerization of HCN (1 molar) in the presence of added formaldehyde (0.5 molar) produced an order of magnitude more 8-hydroxymethyladenine than adenine or any other biologically significant purine. This result suggests that on the prebiotic earth, nucleoside analogs may have been synthesized directly in more complex mixtures of HCN with other aldehydes.

Schwartz, Alan W.↗

Template-directed oligomerization catalyzed by a polynucleotide analog

A pyrophosphate-linked analog of polycytidylic acid has been synthesized and shown to catalyze the oligomerization of the complementary monomer 2'-deoxyguanosine 3',5'-bisphosphoimidazolide. Analogs of polynucleotides are of interest in studies of the origins of life as possible precursors of the first RNA molecules. These results demonstrate that such molecules are capable of serving as templates for further synthesis.

Visscher, J.↗

Oligomerization of deoxynucleoside-biphosphate dimers - Template and linkage specificity

The oligomerization of the activated 3-prime-5-prime pyrophosphate-linked dimer, pdAppdAp, is presently noted to be selectively favored by a poly(U) template over the 3-prime-3-prime and 5-prime-5-prime linked dimers. Both overall yields and the production of the longest oligomers were markedly stimulated by poly(U)'s presence; in its absence, the 5-prime-5-prime linked dimer became the most reactive, yielding chains of the order of 60 monomer-unit lengths. Remarkable self-organization properties are noted for the 5-prime-5-prime dimer of pdAp.

Visscher, J.↗

The case for an ancestral genetic system involving simple analogues of the nucleotides

The idea that the first living systems on earth were based on self-replicating RNA molecules has recently become popular as a result of the discovery of ribozymes. However, there are several major problems associated with the prebiotic synthesis of ribonucleotides. In addition, there is the newly recognized problem of enantiomeric cross-inhibition, whereby template-directed polymerization involving one enantiomer of RNA is inhibited strongly by the presence of the other enantiomer. Here, it is proposed that RNA was preceded in the evolution of life by a polymer constructed from flexible, acyclic, probably prochiral nucleotide analogues that were synthesized readily on the primitive earth. Several potentially prebiotic nucleotide analogues are considered in this context, and some of the consequences of this proposal are discussed.

Joyce, Gerald F.↗

Analysis of a fixed-pitch X-wing rotor employing lower surface blowing

Lower surface blowing (LSB) is investigated as an alternative to the variable blade pitch requirement for the X-wing Circulation Control (CC) rotor concept. Addition trailing edge blowing slots on the lower surfaces of CC airfoils provide a bidirectional lift capability that effectively doubles the control range. The operational requirements of this rotor system are detailed and compared to the projected performance attributes of LSB airfoils. Analysis shows that, aerodynamically, LSB supplies a fixed pitch rotor system with the equivalent lift efficiency and rotor control of present CC rotor designs that employ variable blade pitch. Aerodynamic demands of bidirectional lift production are predicted to be within the capabilities of current CC airfoil design methodology. Emphasis in this analysis is given to the high speed rotary wing flight regime unique to stoppable rotor aircraft. The impact of a fixed pitch restriction in hover and low speed flight is briefly discussed.

Schwartz, Alan W.↗

Nucleic acid-like structures. II - Polynucleotide analogues as possible primitive precursors of nucleic acids

Activated derivatives of purine-containing deoxynucleoside- diphosphates spontaneously oligomerize to produce pyrophosphate- linked oligodeoxynucleotide analogs. These analogs are of potential interest as models of primitive, polynucleotide precursors. The efficiency of oligomerization (ImpdGpIm and ImpdApIm much greater than ImpdIpIm) appears to reflect a combination of stacking forces and the specific geometric orientations of the stacked units. Under favorable conditions, chain lengths greater than 20 have been obtained for oligomers containing pdGp in the absence of a template. In the presence of a complementary template, the activated derivatives of pdGp and pdAp oligomerize much more extensively. An acyclo-analog of G has also been shown to undergo template-directed oligomerization on poly(C). These observations suggest the possibility that primitive information transfer might have evolved in much simpler systems and that this function was taken over by polynucleotides at a later stage in evolution.

Schwartz, Alan W.↗