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The Francis Crick Papers

Letter from Leslie E. Orgel to Francis Crick pdf (112,325 Bytes) transcript of pdf
Letter from Leslie E. Orgel to Francis Crick
Number of Image Pages:
2 (112,325 Bytes)
1973-12-11 (December 11, 1973)
Orgel, Leslie E.
Crick, Francis
Original Repository: Wellcome Library for the History and Understanding of Medicine. Francis Harry Compton Crick Papers
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Reproduced with permission of Leslie E. Orgel.
Exhibit Category:
Embryology and the Organization of DNA in Higher Organisms, 1966-1976
Metadata Record Letter from Francis Crick to Leslie E. Orgel (December 19, 1973) pdf (144,849 Bytes) transcript of pdf
Box Number: 13
Folder Number: PP/CRI/D/1/2/10
Unique Identifier:
Document Type:
Letters (correspondence)
Physical Condition:
Series: Correspondence
SubSeries: Alphabetical Correspondence
SubSubSeries: Correspondence 2
Folder: Correspondence: O
December 11, 1973
Dear Francis:
I am writing for a change about science rather than about Dipenidam. Two questions have come up in work on non-enzymatic DNA synthesis, which I feel you will be able to answer much better than anyone here.
In general, if a nucleotide analogue can be incorporated into an oligonucleotide on a polynucleotide template P, then it should be possible to use that analogue as a component of a complementary template P'. There is one obvious reservation, namely that the analogue have sites equivalent to both the 3' and the 5' ends of a standard nucleotide, but everything else should be taken care of by the diad axes of the double helix. Can this obvious notion be made more precise by some stronger (symmetry) argument?
The second question is raised by the difficulty of separating double-stranded structures, once they have been formed. The standard answer is that a cycle of heating and cooling is required-separation occurs at high temperatures and synthesis at low. A totally different approach is to suggest that the double-stranded forms of the earliest "nucleic acid" molecules were much less stable than contemporary nucleic acids, but that the association of monomers or very short oligomers with the original single-stranded "polynucleotides" was as stable as in the contemporary system. One requires a structure in which the first few base pairs form nicely, but stereochemical or other constraints make indefinite extension difficult or impossible. Can you comment on how this could most easily be done, and also on the relevance of the symmetry of the double helix to the problem of achieving an appropriate "misfit"?
Yours sincerely,
Leslie E. Orgel
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