Saenger, W.

Scheit, K.H.

Suck, D.

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Volume 5, number 4 FEBS LETTERS November 1969 
CRYSTAL AND MOLECULAR STRUCTURE OF 3’-O-ACETYL-2’- 
DEOXYd-THIOTHYMIDINE 
WSAENGER, D. SUCK and K.H.SCHEIT 
Mox-Planck-Institut f& experimentelle Medizin, Abteilung Chemie, 
Gtittingen, Germany 
Received 18 October 1969 
1. Introduction 
When deoxy4-thiothymidine-5’-triphosphate (ds 
4TTP) was substituted for deoxythymidine-S’-triphos- 
phate (dTTP) in the enzymatic synthesis of poly d 
(A-T) by DNA-polymerase the formation of poly d 
(A-s4T) could be demonstrated [l] . Poly d (A-s4T) 
was a poor primer for the synthesis of poly d (A-T) 
but did not serve as template if dTTP was replaced by 
ds4TTP. This different behaviour of poly d (A-s4T) 
and poly d (A-T) towards DNA-polymerase iniated a 
thorough investigation of the physical properties of 
deoxy4-thiothymidine derivatives. In this paper the 
crystal and molecular structure of 3’-0acetyl-2’- 
deoxy4-thiothymidine isreported. 
2. Materials and methods 
Yellow prismatic rystals were obtained by slow 
evaporation of an aqueous olution of 3’-acetyl-rlthio- 
thymidine. Space group and cell dimensions of these 
crystals were P2,212, and a = 13.578 A, b = 5.175 A, 
c = 19.667 A. The intensities of 1084 reflections were 
measured on a four circle diffractometer using Cu-ra- 
diation and corrected for geometrical factors but not 
for absorption. The structure was solved from a series 
of Patterson and Fourier syntheses and after several 
cycles of anisotropic least squares refinement adiffe- 
rence Fourier synthesis revealed the positions of all 
the hydrogen atoms. The final R-factor was 5.4%. 
262 
3. Results and discussion 
In the figure, bond distances and angles within the 
molecule are given. 
The geometrical data of the heterocycles are in 
reasonable agreement with the values found for I- 
methylthymine [2] and Ca thymdidilate [ 31. The 
bonds C5C6, C2-02 and C-S of 1.333 A, 1.211 A 
and 1.673 A length have double bond character. The 
arrangement of the atoms and substituents of the py- 
rimidine ring system is essentially planar except atom 
Cl’ , which is displaced by 0.124 W from the plane. 
The five membered eoxy-ribose ring is puckered 
with C2’ endo (envelope form): C2’ is 0.526 A away 
from the best four atom plane. All the angles, dihedral 
angles and distances compare well with the correspon- 
ding values published for 5-fluoro-2’deoxy+uridine 
[4] ercept the bond length C3’C4’ which is increased 
by 0.05 A. The conformation about the C4’C5’ and 
the C3’03’ bond is gauche. The acetyl group is lying 
in a plane almost perpendicular to the deoxyribose 
ring. 
The heterocycle of a nucleoside can take two pre- 
ferred conformations with respect o the sugar moiety 
which are called syn and anti [5] depending upon the 
position of the oxygen atom 02 relative to the ribose, 
i.e. upon TCN, the dihedral angle C2’C 1 ‘-N 1 C6 [6] . 
In the syn conformation 02 is above or near the sugar 
residue and TcN is 0 to 180’ whereas is the anti con- 
formation 02 is away from the ribose and 7CN is to 
-180’. In 3’-acetyl4thiothymidine CN is -63.7’, i.e. 
its conformation is anti. 
This result is striking. 4_Thiouridine, an analogous 
molecule, crystallizes in vn conformation [7], TcN = 
139”, but could be shown by NMR and ORD studies 
North-Holland Publishing Company - Amsterdam 
Volume 5, number 4 FEBS LETTERS November 1969 
I 
” 
Volume 5, number 4 FEBS LETTERS November 1969 
to exist in anti conformation [8] in aqueous olution. from anti to syn depends upon the development of a 
The reason for this conformational change of Cthiou- hydrophobic-hydrophilic structure but we feel that 
ridine could be found in its peculiar crystal structure. some more data are needed to support hat idea. 
The 3’-acetyl4thiothymidine molecules are stacked 
along the crystallographic b-axis, the heterocycle being 
parallel to each other in a distance of 3.68 A and tilted 
about 44.7’ against the b-axis. The molecules are of 
hydrophobic haracter and there is only one hydrogen 
bond of 3.227 A length from the sulfur to the 05’- 
oxygen atom. 
Acknowledgements 
The molecules of 4-thiouridine are also arranged in 
stacks but the heterocycles are perpendicular to a 
crystallographic axis and 3.4 A apart. They constitute 
a linear hydrophobic hannel whereas the ribose moie- 
ties together with 1.5 molecules of water of hydration 
per nucleoside unit build up a hydrophilic channel. 
We thank Prof. Cramer for his interest and the sup- 
port of our studies. We are grateful to Prof. D.Mootz, 
Universitit Braunschweig, for making his Siemens dif- 
fractometer available to us for the data collection. 
References 
The differences in the structures of 3’-acetyl4thio- 
thymidine and 4-thioridine are anti conformation and 
hydrophobic haracter of the molecules’for the first 
and syn conformation and the arrangement of hydra 
phobic-hydrophilic channels for the second structure. 
One could suspect hat the conformational change 
[l] A.G.Lezius and K.H.Scheit, European J.Biochem. 3 (1967) 
[ 21 &oogsteen, Acta Cryst. 16 (1963) 28. 
[ 31 K.N.Trueblood, P.Horn and V.Luzatti, Acta Cryst. 14 
(1961) 965. 
[4] D.R.Harris and W.H.Macintyre, Biophys. J. 4 (1964) 203. 
[5] J.Donohue and K.N.Trueblood, J. Mol. Biol. 2 (1960) 
369. 
[6]WSaenger and K.H.Scheit, J. Mol. Biol. in press. 
[7] W.Saenger and K.H.Scheit, Angew. Chem. 81(1969) 121. 
[8] K.H.Scheit and W.Saenger, FEBS Letters 2 (1969) 305. 
264 


Crystal and molecular structure of 3′-O-acetyl-2′-deoxy-4-thiothymidine 

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Crystal and molecular structure of 3′-O-acetyl-2′-deoxy-4-thiothymidine

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