title: Ribonucleotides.
abstract: It has normally been assumed that ribonucleotides arose on the early Earth through a process in which ribose, the nucleobases, and phosphate became conjoined. However, under plausible prebiotic conditions, condensation of nucleobases with ribose to give beta-ribonucleosides is fraught with difficulties. The reaction with purine nucleobases is low-yielding and the reaction with the canonical pyrimidine nucleobases does not work at all. The reasons for these difficulties are considered and an alternative high-yielding synthesis of pyrimidine nucleotides is discussed. Fitting the new synthesis to a plausible geochemical scenario is a remaining challenge but the prospects appear good. Discovery of an improved method of purine synthesis, and an efficient means of stringing activated nucleotides together, will provide underpinning support to those theories that posit a central role for RNA in the origins of life.
authors.affiliation: The University of Manchester, United Kingdom. john.sutherland@manchester.ac.uk <john.sutherland@manchester.ac.uk>
authors.forename: John D
authors.initials: JD
authors.lastname: Sutherland
mesh_terms: D019418:Evolution, Chemical; D000069497:Origin of Life; D012265:Ribonucleotides / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics
chemical_list: D012265:Ribonucleotides
references.citation: Biochemistry. 1970 Dec 8;9(25):4907-13
references.pmid: 5480155
references.citation: Org Biomol Chem. 2005 May 21;3(10):1850-5
references.pmid: 15889167
references.citation: Nature. 2009 May 14;459(7244):171-2
references.pmid: 19444196
references.citation: J Mol Evol. 1973 Nov 27;2(4):303-16
references.pmid: 4377773
references.citation: Orig Life. 1976 Dec;7(4):399-412
references.pmid: 1023139
references.citation: Science. 1966 Nov 11;154(3750):784-5
references.pmid: 5919447
references.citation: J Mol Biol. 1967 Dec 14;30(2):223-53
references.pmid: 4297187
references.citation: J Org Chem. 2002 Feb 8;67(3):790-802
references.pmid: 11856021
references.citation: Orig Life Evol Biosph. 1988;18(1-2):71-85
references.pmid: 2453009
references.citation: Chem Biodivers. 2004 Oct;1(10):1418-51
references.pmid: 17191788
references.citation: Nature. 2001 Jan 18;409(6818):387-90
references.pmid: 11201752
references.citation: Science. 1968 Jul 5;161(3836):64-6
references.pmid: 5655266
references.citation: Science. 2004 Jan 9;303(5655):196
references.pmid: 14716004
references.citation: Crit Rev Biochem Mol Biol. 2004 Mar-Apr;39(2):99-123
references.pmid: 15217990
references.citation: Angew Chem Int Ed Engl. 2007;46(14):2354-6
references.pmid: 17285673
references.citation: Chem Commun (Camb). 2006 Jun 14;(22):2344-6
references.pmid: 16733574
references.citation: J Phys Chem A. 2006 Mar 23;110(11):4012-20
references.pmid: 16539424
references.citation: Nature. 2009 May 14;459(7244):239-42
references.pmid: 19444213
references.citation: Chembiochem. 2008 Oct 13;9(15):2386-7
references.pmid: 18798212
references.citation: Chem Biodivers. 2005 Jan;2(1):66-83
references.pmid: 17191920
references.citation: Nature. 1996 May 2;381(6577):59-61
references.pmid: 8609988
references.citation: J Mol Evol. 1972;1(3):249-57
references.pmid: 4681226
references.citation: Nature. 1971 May 7;231(5297):42-3
references.pmid: 4930470
references.citation: Proc Natl Acad Sci U S A. 1968 Jan;59(1):34-8
references.pmid: 16591589
references.citation: Chemistry. 2008;14(8):2375-88
references.pmid: 18203227
references.citation: J Mol Biol. 1968 Dec;38(3):367-79
references.pmid: 4887876
references.citation: Astrobiology. 2005 Aug;5(4):515-35
references.pmid: 16078869
references.citation: Angew Chem Int Ed Engl. 2006 Sep 18;45(37):6176-9
references.pmid: 16917794
references.citation: Chembiochem. 2005 Nov;6(11):1980-2
references.pmid: 16172991
references.citation: Chembiochem. 2003 Jun 6;4(6):504-7
references.pmid: 12794860
references.citation: J Mol Biol. 1968 Dec;38(3):381-93
references.pmid: 5718557
references.citation: J Am Chem Soc. 1968 Mar 13;90(6):1678-9
references.pmid: 5636808
references.citation: Science. 1953 May 15;117(3046):528-9
references.pmid: 13056598
references.citation: Science. 1971 Feb 5;171(3970):490-4
references.pmid: 5099649
references.citation: Proc Natl Acad Sci U S A. 1987 Jul;84(13):4398-402
references.pmid: 2440020
references.citation: Philos Trans R Soc Lond B Biol Sci. 2006 Oct 29;361(1474):1681-7
references.pmid: 17008209
references.citation: Chembiochem. 2007 Jul 9;8(10):1170-9
references.pmid: 17549787
references.citation: J Am Chem Soc. 2005 Mar 30;127(12):4174-5
references.pmid: 15783191
references.citation: J Mol Biol. 1970 Feb 14;47(3):531-43
references.pmid: 5418170
references.citation: Science. 1999 Jun 25;284(5423):2118-24
references.pmid: 10381870
references.citation: Chem Biodivers. 2004 Feb;1(2):203-46
references.pmid: 17191842
references.citation: Science. 2000 Nov 17;290(5495):1347-51
references.pmid: 11082060
references.citation: Nature. 2002 Jul 11;418(6894):214-21
references.pmid: 12110897
references.citation: Chem Biodivers. 2007 Apr;4(4):721-39
references.pmid: 17443885
references.citation: Nature. 1995 Jun 29;375(6534):772-4
references.pmid: 7596408
references.citation: J Mol Biol. 1968 May 14;33(3):693-704
references.pmid: 5700419
references.citation: J Mol Biol. 1972 Jun 14;67(1):25-33
references.pmid: 4339529