Table Of ContentRef. p. 211 1.1 Abbreviations and symbols
1 Nomenclature, definitions and geometry
of basic structure elements
In the past, several independent definitions were used to describe the structural parameters of the nucleic
acids and of their constituents. There have been two major proposals made by the “IUPAC-1UB Commission
on Biochemical Nomenclature“‘) which will be followed throughout this volume. One, concerned with the
chemical nomenclature dates back to 1970 [7011], the other is much more recent, 1983, and used to describe
the three-dimensional structure of nucleosides, nucleotides and nucleic acids [8311].
1.1 Abbreviations and symbols
There are two kinds of nucleic acids,
ribonucleic acid (RNA) and
deoxyribonucleic acid (DNA).
The nucleic acids are linear polymers composed of four different building blocks, the nucleotides, which
are linked by phosphodiester bonds. The individual nucleotide consists of a furanoside-type ribose (in RNA)
or 2’-deoxyribose (in DNA) connected by a Cl’-N glycosyl bond with one of four different bases, and
by ester bond(s) to a phosphate group (Tables 1 and 2, Fig. 1).
H\../H
G
u
c
Fig. 1. Fragment of ribonucleic acid (RNA) with sequence adenosine (A), guanosine (G), uridine (U), cytidine (C) linked
by 3’,5’-phosphodiester bonds. Chain direction is from 5’- to 3’-end as shown by arrow. Atom numbering scheme is
indicated in one framed nucleotide unit, 5’-GMP. All hydrogen atoms are drawn in A and only functional hydrogens
in other nucleotides. In short notation, this fragment would be pApGpUpCp or pAGUCp. In deoxyribonucleic acid
(DNA), the hydroxyl attached to C2’ is replaced by hydrogen and uracil, by thymine [84Sl].
‘) IUPAC = International Union of Pure and Applied Chemistry. IUB = International Union of Biochemistry.
Land&-Biimstein Saenger ‘1
New Series VU/l a
1.1 Abbreviations and symbols [Ref. p. 21
Table 1. The constituents of nucleosides and nucleotides.
adenine
Purine
guanine
Base
cytosine
I “=Yymr idine
uracil (in RNA), thymine (in DNA)
D-ribose (in RNA)
Nucleoside = Base+ Sugar
2’-deoxy-D-ribose (in DNA)
linked by phosphodiester bond at
Nucleotide = Base+ Sugar + Phosphate 2’,3’ or 5’ hydroxyl in RNA
3’ or 5’ hydroxyl in DNA
Table 2. Abbreviations and symbols for bases,n ucleosides, and nucleotides’).
Base Nucleoside Nucleotide
Name Symbol Name Symbol Name Symbol
Ribonucleosides and -nucleotides
Uracil Ura uridine Urd or U uridylic acid S-UMP or pU
Cytosine CYt cytidine Cyd or C cytidylic acid S-CMP or pC
Adenine Ade adenosine Ado or A adenylic acid S-AMP or pA
Guanine Gua guanosine Guo or G guanylic acid S-GMP or pG
2’Deoxyribonucleosides and -nucleotides2)
Thymine Thy deoxythymidine3) dThd or dT deoxythymidylic acid S-dTMP or pdT
Cytosine CYt deoxycytidine dCyd or dC deoxycytidylic acid S-dCMP or pdC
Adenine Ade deoxyadenosine dAdo or dA deoxyadenylic acid S-dAMP or pdA
Guanine Gua deoxyguanosine dGuo or dG deoxyguanylic acid S-dGMP or pdG
Other examnles
Nucleotides2) Polynucleotides
uridine 2’-monophosphate (2’-UMP) polyadenylic acid (poly A); alternate copolymer
uridine 3’-monophosphate (3’~UMP, Up) of dA and dT, poly(deoxyadenylate-deoxy-
cytidine diphosphate (CDP, ppC) thymidylate), poly [d(A-T)], or poly(dA-dT)
cytidylyl-(3’S)-uridine (CPU) or (dA-dT), or d(A-T),; the same but randomly
adenosine triphosphate (ATP, pppA) distributed dA, dT: replace hyphen by comma,
guanosine 2’,3’-cyclic phosphate poly d(A, T) etc. A complex between poly(A)
(2’,3’-GMP, G >p, cGMP) and poly(U) is designated poly(A).poly(U)
alanine-specific transfer RNA from E. coli
(tRNA*‘“(E. co/i))
‘) Adapted from [70Al], taken from [84Sl].
‘) The symbols for 2’-deoxyribonucleosides and -tides are as for ribonuclcosides and -tides with the prefix d.
3)Since thymidine occurs as a ribonucleoside in tRNA, use of the pretixes d for deoxyribose and r for ribose is
recommended [7011].
I”
2 Saenger
a
Ref. p.211 1.1 Abbreviations and symbols
I) Basesa nd nucleosides
In the atom designation, base atoms are described by letter and numerals with or without parentheses,
:.g. N(9), N9 or N,, and sugar atoms are distinguished by primed numerals, e.g. C(2), C2’ or C,..
The free purine bases adenine, guanine bear a hydrogen atom at position 9, which in the nucleosides
.s substituted by Cl’ of ribose or deoxyribose in a p-type glycosyl link (Fig. 2). The same holds for the
‘ree hydrogen atom in position 1 of the pyrimidine basesc ytosine, uracil (in RNA) or the equivalent thymine
:in DNA).
b) Nucleotides
Nucleosides can be phyosphorylated in three (ribose) or two (deoxyribose) sugar hydroxyl positions to form
a number of different nucleotides :
nucleoside-S-phosphate
nucleoside-3’-phosphate
ribo-nucleoside
nucleoside-2’-phosphate
I etc.
deoxyribonucleoside-S-phosphate
deoxyribo-nucleoside deoxyribonucleoside-3’-phosphate
i etc.
Nucleosides can also be di- or triphosphorylated (see Fig. 2):
diphosphorylated at two positions, e.g.:
adenosine-3’,5’-diphosphate, A-3’,5’-P,, or A-3’: 5’-P,, or 3’,SADP, or pAp
di- or triphosphorylated at one position, e.g.:
adenosine-5’-diphosphate, ADP
adenosine-5’-triphosphate, ATP.
The phosphate can be attached to two hydroxyls of the same nucleoside to form a cyclic phosphate (Fig. 2),
e.g.:
adenosine-3’,5’-cyclic phosphate, Ado-3’,5’-P, Ado-3’: S-P, 3’,5’-AMP, A > p, CAMP
adenosine-2’,3’-cyclic phosphate, Ado-2’,3’-P, Ado-2 : 3’-P, 2’,3’-AMP, A > p, CAMP.
A special case is the coenzyme nicotinamide-adenine-dinucleotide, NAD+, which contains nicotinamide ribo-
side (Nir) and Ado separated by a pyrophosphate group: Ado-S’PPS-Nir.
c) Oligo- and polynucleotides
These are designated with the one-letter code (Table 2) with prefix d if in the DNA series. The “polarity”
is in the direction 5’+3’ (Fig. l), if not otherwise indicated. The phosphodiester linkage is the common
3’pS, and is specified if different.
The oligonucleotide guanylyl-3’,5’-cytidylyl-3’,5’-uridine can be abbreviated GpCpU or, shorter G-C-U
or GCU, with G the S-end and U the 3’-end of the chain.
If the oligomer contains terminal phosphate groups, these are specified:
ApGpUp (or A-G-Up or AGUp) has a 3’-terminal phosphate
ApGpU > p (or A-G-U > p or AGU > p) has a terminal 2’3’ (or 2’: 3’) cyclic phosphate
pApGpU (or PA-G-U or pAGU) has a 5’-terminal phosphate
dApdGprCprU (or dApdGpCpU or dAdGCU or d(AG)r(CU))
contains deoxyribo- and ribonucleotides in the same oligomer.
In the base-paired complementary oligonucleotides, the nomenclature is:
ACUAGC
UGAUCG
or A+C+U+A+G+C
UcGcAcUtC+G
or AP CP UP AP GP C
UP GP AP UP CP G
Land&B6rnstein
3
New Series VII/l a
1.1 Abbreviations and symbols [Ref. p. 21
In the deoxyribo series,t he prefix d is used but it can be omitted if it is not necessary:
d (pGATCGAT) or pGATCGAT.
In polymer nucleic acids which are mostly obtained synthetically, the prefix poly is used, meaning “polymer
DT’:
polyadenylic acid or polyadenylate or poly(A)
alternating copolymer po!y(adenylate-cytidylate): poly(A-C)
random copolymer of the same type poly(A,C).
In the deoxy series,t he prefix d is used :
poly(dA); and for the alternating copolymer: poly[d(A-T)] or poly(dA-dT).
Complementary duplex formation is indicated by a dot symbol poly(A).poly(U) and a triple helix is:
poly(A)=2poly(U). The alternating copolymer duplex in the deoxyribonucleoside series is described as:
poly[d(G-C)J.poly[d(G-C)], or poly(dG-dC).poly(dGdC).
d) Modified basesa nd sugars
Basesa nd sugars can be modified by different substituents in different positions.
The substituents are abbreviated as:
m, e, ac methyl, ethyl, acetyl
CC aza (N replaces C), deaza (C replaces N)
h dihydro (hU = dihydrouridine)
hm, ho (or oh) hydroxymethyl, hydroxy
aa aminoacyl
f formyl
i isopentenyl
S thio or mercapto (sU = thiouridine)
fl, cl, br, io fluoro, chloro, bromo, iodo.
The positions are indicated by superscripts, multipliers by subscripts. Some examples:
m,A dimethyladenosine or N6-dimethyladenosine
m:A ribosyL6-(dimethylamino)purine
ac4C N’-acetylcytidine
SW 2-thiouridine.
Frequently, riboses are methylated at the 02’ position, The prefix 2’-O-Me is used, or replaced by
the suffix m, e.g.: 2’-0-MeC is written as Cm.
odenine guonine cytosine urocil thymine
Ade Guo CY{ Ur0 W
4 Saenger
Ref. p. 211 1.1 Abbreviations and symbols
uridine deoxyodenosine orobinocytidine
Urd,U dAdo,dA oroCyd,oroC
I
odenylic ocid,5’-AMP,pA,
adenosine- 5’-phosphate 0,6-O, OTP-OH
0 \I 0 :I
0 b
odenosine-3’-phosphate odenosine- 3’. 5’- di-
3’-AMP.Ap phosphote,3’,5 ’-AOP,pAp
OH OH
odenosine -5’- diphosphote,AOP,ppA
HO
0\3’ ,021
P
,&\, 0
odenosine- 2’,3’-cyclic phosphate, odenosine- 3’,5’-cyclic phosphate
cyclic phosphote.2’,3’-AMP.A*P 3’. 5’- AMP,“ cyclic AMP”
OH OH
nicotinomide odenine dinucleotide NAD’
Fig. 2. Chemical structure of some bases, nucleosides, nucleotides and the coenzyme NAD+ [84Sl]. The word arabino
describes the sugar moiety which is derived from the arabinose. In this context, all the nucleosides could be described
more fully as e.g. ribouridine or deoxyribouridine. Because the common nucleosides are of the ribo form, the word ribo
is usually omitted in the nomenclature.
Saenger 5
1.2 Description of conformation [Ref. p. 21
1.2 Description of conformation
a) Bond distances, bond angles, torsion angles
T’he three-dimensional structure of any molecule can be described by:
bond distances A-B between two covalently bound atoms A,B
bond angles A-B-C between three covalently bound atoms A,B,C
torsion angles, which give the relative orientation of four covalently bound atoms A-B-C-D.
For the torsion angles, the IUPAC-IUB commission has recommended the following definition [8311]:
The torsion angle 8 in Fig. 3 is described as the angle between projected bonds A-B and C-D when
looking along the central bond either in direction B+C or in the opposite sense C-B. It is defined as
0” if A-B and C-D are eclipsed (cis and coplanar), and the sign of 0 is positive if the front bond A-B
(if looking in direction B-C) has to be rotated clockwise to eclipse it with the rear bond C-D. If it has
to be rotated anti-clockwise, 0 is negative. The torsion angle 0 is reported either in the range 0” to 360”
or - 180” to + 180”.
Rather than describing the torsion angle 8 in terms of an angle between projected bonds, it can also
be formulated as an angle between the two planes containing atoms, A, B, C, and B, C, D. Another definition
uses the angle between the normal to these planes. This dihedral angle (Fig. 3) is in fact the complement
of the torsion angle 8. In the literature, the nomenclature torsion and dihedral angles are often confused,
as are the definitions, and the term “dihedral angle” is used to describe, in fact, a torsion angle. Therefore,
one has to be careful if reading the literature.
Becauser otations about bonds are usually restricted by steric requirements, it is often sufficient to describe
a molecular conformation by a torsion angle range rather than by the proper torsion angle. The ranges
commonly used in organic chemistry are those proposed by Klyne and Prelog, syn (ZOO), anti (w 1809,
+ synclind (us +_6 0”), and + anticlinal (x f 120”) [60K 11. In spectroscopic and crystallographic publications,
the notation cis (zoo), tram (z 1807, + gauche (w * 60”) is most frequently employed (Fig. 4).
Fig. 3a...d. Definition of torsion and dihedral angles. (a)
Torsion angle0 (A-EC-D) describingo rientationso f bonds
B.C A-B and C-D with respect to the central bond B-c. (b)
b View along B+C. ti is the torsion angle between the pro-
jected bonds A-B and C-D; the complement 4 is called
the dihedral angle. If A-B and C-D are cis-planar (coin-
ciding in projection), angles O=O” and 4 = 180” (O= 180”~4);
they are counted positive if the near bond A-B has to be
rotated clockwise to bring it into cis-planar position with
the far bond C-D. (c) 0 is defined as the angle between
planesA -B-C and B-C-D. (d) The dihedral angle4 repre-
sents the angle between normals to these planes [84SI].
Note: in the literature, the terms “torsion” and “dihedral”
are often confused and used synonymously. Most frequently
“dihedral” means angles defined as 0 in Fig. 3, which are,
in fact, “torsion” angles.
6 Saenger
Ref. p. 211 1.2 Description of conformation
cis
Fig. 4. Correlation of torsion angle ranges (cis, tram, +gauche, -gauche) with ranges defined by Klyne and Prelog [60Kl]
(syn or synperiplanar, anti or antiperiplanar, +synclinal, -synclinal, +antidinal, -anti&al). The terms syn, anti have
a special meaning in nucleotide stereochemistry (Fig. 8) [84Sl].
b) Definition of the nucleotide unit
A nucleotide unit is the repeating unit of a polynucleotide chain, and defined by the sequence of atoms
from the phosphorous atom at the S-end to the oxygen atom at the 3’-end of the pentose sugar (Fig. 5).
c) Definition of backbone torsion angles in the nucleotide unit
The repeating unit of the backbone of a polynucleotide chain consists of six bonds as shown in Fig. 5:
PW, OS-C5’, CS-Cl’, C4’-C3’, C3’-03’, 03’-P. The torsion angles about these bonds are denoted by
greek symbols in sequential and in alphabetical order: GI,/ I, y, 6, E, c. In another notation, the nomenclature
used in polypeptides was adapted, as: o, r#~I,+ +I,+ V,@ , w’, but was not recommended by the IUPAC-IUE
commission [8311]. It is, however, still in use in some laboratories.
d) Endocyclic and exocyclic sugar torsion angles
In nucleic acids, the furanose sugar ring is part of both the backbone and the sugar-base side-chain
The conformation of the sugar is described by the endocyclic torsion angles for the bonds O&Cl’, Cl’C2’.
C2’-CY, C3’-C4’, C&04’, which are denoted by the symbols va, vr, v 2, va, v4, respectively (Fig. 5).
The backbone torsion angle 6 and the endocyclic sugar torsion angle vg refer to the same bond C3’-C4’
but one is exocyclic, the other endocyclic. They are both needed to properly describe the nucleotide conforma-
tion.
In oligonucleotide crystal structure analyses, it is common usage to describe the sugar pucker only
with the exocyclic torsion angle 6, defined by C5’-C4’-C3’43’. Although this might be sufficient in an
ideal system with undistorted bond geometry, its use should be discouraged in favor of the better and
more reliably defined pseudorotation parameters given in subsections (e) and (l). They can be easily derived
once the atomic coordinates of an oligonucleotide are known.
Land&Bb;mstein
New Series VII/l a Saenger
1.2 Description of conformation [Ref. p. 21
chain
In - 1) direction
nucleotide
unit n
i --.
in+11
Fig. 5. Atomic numbering scheme and defmition of torsion
angles for a polyribonucleotide chain (arrows indicate posi-
tive rotation of angles A-B-C-D when looking along the
central bond B+C given in the table). Counting of nucleo-
tides is from top to bottom, i.e., in the direction OS-t03’.
Hydrogens at C5’ are differentiated by 1 and 2. In deoxyri-
bose, the hydrogen replacing 02 is labelled 2, the other
one, 1. The full description of torsion angles is given in the
following table [84Sl].
Torsion angle Atoms involved’)
(” - ,,OY-P-OS-C5
P-05’-W-C4
OS-W-W-C3
cs-W-C3’-03’
c4’-C3’-03’-P
cY-O3’-P-O5;, + * )
04’-CI’-Nl-C2 (pyrimidines)
04’-Cl’-N9-C4 (purines)
“0 C4’04-c II-C2
“1 04’-Cl’-CL!-c3
“2 Cl’-W-c3’c4
VI) c2’-c3’-c&04
c3’-c4’-04’-C1’
v4
‘) Atoms designated (n - 1) and (n + 1) belong to adja-
cent units.
Iandolt-EGmstcin
8 Saenger New S&s VII!1 a
Ref. p. 211 1.2 Description of conformation
e) Description of sugar pucker
The sugar ring is generally puckered such that in the envelope (E) conformation one ring atom deviates
from the plane defined by the other four atoms, or in the twist (T) conformation two atoms deviate from
the plane defined by the other three atoms (Fig. 6a, b). The pucker is described relative to the exocyclic
atom CS, and called endo if the puckered atom is on the same side of the plane as CS’, otherwise exo.
Thus, if atom C3’ is on the same side as CS in an envolope form, the pucker is described as
C3’-endo or 3E (with a 3 preceding E as a superscript) and if it is on the opposite side, we have
C3’-exo or 3E (with a 3 preceding E as a subscript).
In the twist form, the twist can be symmetrical, e.g.:
C3’-endo, CT-exo or QT,
but it can also be unsymmetrical, with more pronounced C2’-exo than C3’-endo pucker. Then the major
pucker atom precedest he letter T (as sub- or superscript) and the minor pucker atom follows, e.g.:
C2’-exo, CY-endo, or 2T3 (major pucker is C2’-exo, minor pucker is C3’-endo).
a
(i) (iy”)& J
(ii) (“c) $&iNJ
2'
(iii)
b
Fig. 6a, b. (a) Puckering of tive-membered ring into envelope (E) and twist (T) forms. In E, four of the five atoms are
coplanar and one deviates from this plane; in T, three atoms are coplanar and the other two lie on opposite sides of
this plane. Lb) Definition of sugar puckering modes. (i) Starting position with flat five-membered sugar, a situation never
observed. Plane C1’-04’-C4’ is shown hatched. (ii ... v) View with this plane perpendicular to the paper. (ii) Envelope
C3’-endo, 3E. (iii) Envelope C2’-endo, ‘E. (iv) Symmetrical twist or half-chair C2’-exo, C3’-endo, :T. (v) Unsymmetrical
twist with major C3’-endo and minor C2’-exo pucker, “T, [84Sl].
andolt-Bhstein
lew Series VII/l a Saenger 9
1.2 Description of conformation [Ref. p. 21
f) Pseudorotationaal nalysis (Fig. 7a, b)
Each sugar ring conformation can be neatly described by two pseudorotational parameters which can
be derived by mathematical formulae from the five endocyclic torsion angles [72A2, 73A1, 81R1, 85Ml]:
the phase angle of pseudorotation, P, and the degree of pucker, v,,, (called $,,, in [72A2, 73A1, 83111
and t, in [81Rl, 85Ml]), which gives a measure of the maximum out-of-plane pucker of the furanose
ring atoms. The pseudorotation phase angle is defined as 0” if torsion angle Cl’-C%C3’-C4’ is maximally
positive corresponding to the symmetrical form C3’-endo, C2’-exo, or ZT, and P adopts values 0” to 360”.
Conformations in the upper (“northern”) half of the circle (Fig. 7a) (P=O”+900) are denoted N, those
in the lower (“southern”) half of the circle (P= 180”+90”) are denoted S. As illustrated in Fig. 7, envelope
and symmetrical twist pucker modes alternate every 18”, with E at even and T at odd multiples of 18”
of the pseudorotation phase cycle.
For the calculation of P and vmnxrtw o different mathematical equations have been derived. Since different
endocyclic torsion angles Bj and 6; are used which are also different from those described in Fig. 5, one
has to be careful in their application. These equations are:
I. The original formulation [72A2, 73Al]:‘)
(e2+e4)-e4 +w
tan P=
20, (sin 36” + sin 72”)
ej=e,c0s(P+j6) (d=bw)
em= eofcOPs
II. In a new formulation, a Fourier-type equation is used [81Rl, 85Ml]:‘)
A=0.4 i 0;cos[144”(i-l)]
i=l
B= -0.4 i e; sin[144”(i-l)]
i=1
tan P = B/A (if A < 0, then 180” is added to P)
t,=pTiF
In these equations, 6, and 0: are different and they deviate from the IUPAC-IUB recommendation for
the vj (Fig. 5). The necessaryt ranslation table is:
Equation I e3 0, 0, e2
Equation II ek e; e; f-4
IUPAC-IUB vo
Vl VZ v4
This volume vo VI v2 v4
‘)There is an error in the monograph “Principles of Nucleic Acid Structure” [84Sl] concerning the formulae for
vj and vmlX. This will bc corrected in the second print (1988).
2, See also section 2.1.1.4.
Fig. 7a, b. (a) Pseudorotation cycle of the furanose ring in nucleosides. Values of phase angles P given in multiples
of 36”. Envelope E and twist T forms alternate every 18O.A fter rotation by 180” the mirror image of the starting position
is found. On the periphery of the cycle, riboses with signs of endocyclic torsion angles arc indicated. (+)Positive, (-)negative,
(0)angle is 0” [72A2]. (b) Schematic representation of the most frequently observed puckering modes, corresponding to
the pseudorotation. Horizontal transitions are continuous and at the same energy level whereas vertical transitions are
separated by a (shallow) energy barrier and describe an N,‘ S interchange. Note that directions of exocyclic Cl’-N and
C4’-CS’ bondsa rc intrinsically relatedt o sugarc onformation[ 84Sl].
10 Saenger Ncn SeriesV II’1
