Oligonucleotide-directed assembly of materials: Defined oligomers

Article abstract of DOI:10.1021/ja000950k

A nano-architectural system that has high variability while maintaining component specificity is described. Tetraphenylcyclobutadiene(cyclopentadienyl)cobalt complexes and phenyleneethynylene trimers were synthesized and subsequently modified with oligonu

Full text of DOI:10.1021/ja000950k

1828
J. Am. Chem. Soc. 2001, 123, 1828-1833
Oligonucleotide-Directed Assembly of Materials: Defined Oligomers
Shane M. Waybright, Chainey P. Singleton, Kimberly Wachter, Catherine J. Murphy, and
Uwe H. F. Bunz*
Contribution from the Department of Chemistry and Biochemistry, The UniVersity of South Carolina,
Columbia, South Carolina 29208
ReceiVed March 16, 2000
Abstract: A nano-architectural system that has high variability while maintaining component specificity is
described. Tetraphenylcyclobutadiene(cyclopentadienyl)cobalt complexes and phenyleneethynylene trimers were
synthesized and subsequently modified with oligonucleotides utilizing standard phosphoramidite chemistry.
The resulting oligonucleotide modified organics (OMOs) were characterized by UV-vis spectroscopy,
fluorescence spectroscopy, and phosphate analysis. Hybridization of these OMOs resulted in a series of self-
assembled oligomeric hybrids of varying length and topology. These hybrids were characterized by melting
temperature, polyacrylamide gel electrophoresis, and fluorescence spectroscopy. This model system demonstrates
the power of DNA to self-assemble modules of interestsindependent of the module itself.
Introduction
tures. Initial investigations include attaching oligonucleotides
to (a) cyclobutadiene(cyclopentadienyl)cobalt complexes, which
show significant optical properties in an extended system,14a
and to (b) highly fluorescent poly(phenylene ethynylene)s, which
have applications in organic semiconductor devices.14b Subse-
quent hybridization of these oligonucleotide-modified organic
(OMO) moieties results in a system reminiscent of Meijer’s
hydrogen-bonded polymers.15 This self-assembly directed sys-
tem, however, allows for oligomers of defined size by simple
hybridization of its constituents.
In this report, we communicate an initial thrust into creating
novel structures. We demonstrate (1) the incorporation of
organic molecules into oligonucleotides through exploitation of
current oligonucleotide synthesis technology,16 (2) the charac-
terization of these oligonucleotides including methods of
concentration determination, and (3) the hybridization of oli-
gonucleotide-modifed organic (OMO) modules into defined,
oligomeric structures. It is critical to understand that the organic
molecules we use are by no means inclusive, but rather the idea
of oligonucleotides arranging molecules can be extrapolated to
molecules of any researcher’s interest.
The rational construction of nanoscale devices having desired
mechanical, optical, electronic, or other physical properties has
been a major thrust for many researchers.1 Applications of
nanoscale devices are expected in molecular electronics, pho-
tonics, and the field of organic semiconductors. Exploitation
of supramolecular chemistry has generated many exciting
macromolecular architectures. The inherent power of supramo-
lecular forces (hydrogen bonding, π-stacking interactions,
electrostatic interactions, and van der Waals interactions) lies
in their ability to preassemble components and “self-correct”
defects through reversible thermodynamic processes.
For the advancement of nano-science, it is fundamental to
arrange matter on the nanoscale.2 In an effort to create novel
molecular architectures, oligonucleotides are a powerful tool
in assembling structural units in a desired arrangement due to
base specificity, sequence programmability, and stiffness.3
Seeman and co-workers have done extensive work in creating
DNA junctions,4 polygons,5 and polyhedra,6,7 which DiMauro
and Hollenberg8 contend may be useful for electronic circuit
construction through chemical vapor deposition methods. The
groups of Mirkin,9 Schultz,10 and Bergstrom11 have demon-
stratedthe ability of oligonucleotides to arrange the molecules
to which they are attached into supramolecular assemblies.12,13
We aim to further expand and generalize this field by creating
a variety of organic and organometallic hubs, vertices, and
termini that can be linked together forming complex architec-
Results and Discussion
Synthesis of Organic Cores. To facilitate attachment of a
molecule to an oligonucleotide, the molecule should be ap-
(9) Mirkin, C. A.; Letsinger, R. L.; Mucic, R. C.; Storhoff, J. J. Nature
1996, 382, 607. Elghanian, R.; Storhoff, J. J.; Mucic, R. C.; Letsinger, R.
L.; Mirkin, C. A. Science 1997, 277, 1078.
(10) Alivisatos, P. A.; Johnsson, K. P.; Peng, X.; Wilson, T. E.; Loweth,
C. J.; Bruchez, M. P., Jr.; Schultz, P. G. Nature 1996, 382, 609.
(11) Bergstrom, D. E.; Shi, J. Angew. Chem., Int. Ed. Engl. 1997, 36,
111
* To whom correspondence should be addressed. E-mail: bunz@
mail.chem.sc.edu.
(1) Ball, P. Nature 1995, 375, 101.
(2) See July 1999 issue: Chem. ReV. 1999, 99.
(12) For reviews see: (a) Storhoff, J. J.; Mirkin, C. A. Chem. ReV. 1999,
99, 1848. (b) Niemeyer, C. M. Angew. Chem., Int. Ed. Engl. 1997, 36,
585.
(13) An, Y.-Z.; Chen, C.-H. B.; Anderson, J. L.; Sigman, D. S.; Foote,
C. S.; Rubin, Y. Tetrahedron 1996, 52, 5179.
(14) (a) Altmann, M.; Bunz, U. H. F. Angew. Chem., Int. Ed. Engl. 1995,
34, 569. (b) Bunz, U. H. F. Chem. ReV. 2000, 100, 1605.
(15) Sijbesma, R. P.; Beijer, F. H.; Brunsveld, L.; Folmer, B. J. B.;
Hirschberg, J. H. K. K.; Lange, R. F. M.; Lowe, J. K. L.; Meijer, E. W.
Science 1997, 278, 1601.
(16) (a) Caruthers, M. H. Acc. Chem. Res. 1991, 24, 278. (b) Caruthers,
M. H. Science 1985, 230, 281.
(3) Seeman, N. C.; Zhang, Y. J. Am. Chem. Soc. 1992, 114, 2656.
(4) (a) Ma, R.-I.; Kallenbach, N. R.; Sheardy, R. D.; Petrillo, M. L.;
Seeman, N. C. Nucleic Acids Res. 1986, 14, 9745. (b) Petrillo, M. L.;
Newton, C. J.; Cunningham, R. P.; Ma, R.-I.; Kallenbach, N. R.; Seeman,
N. C. Biopolymers 1988, 27, 1337. (c) Wang, Y.; Mueller, J. E.; Kemper,
B.; Seeman, N. C. Biochemistry 1991, 30, 5667.
(5) Chen, J.-H.; Kallenbach, N. R.; Seeman, N. C. J. Am. Chem. Soc.
1989, 111, 6402.
(6) Chen, J.-H.; Seeman, N. C. Nature 1991, 350, 631.
(7) Zhang, Y.; Seeman, N. C. J. Am. Chem. Soc. 1994, 116, 1661.
(8) Di Mauro, E.; Hollenberg, C. P. AdV. Mater. 1993, 5, 384.
10.1021/ja000950k CCC: $20.00 © 2001 American Chemical Society
Published on Web 02/07/2001

Oligonucleotide-Directed Assembly of Materials
J. Am. Chem. Soc., Vol. 123, No. 9, 2001 1829
Scheme 1a
Scheme 2a
a Conditions: (a) PdCl2(PPh3)2/CuI/piperidine; (b) DMTCl/pyridine;
(c) 2-cyanoethyl diisopropylchlorophosphoramidite/diisopropylethyl-
amine/THF.
a Conditions: (a) PdCl2(PPh3)2/CuI/PPh3/NEt3; (b) CpCo(CO)2/p-
xylene; (c) DMTCl/pyridine; (d) 2-cyanoethyl diisopropylchlorophos-
phoramidite/diisopropylethylamine/THF.
propriately functionalized. Thus, cyclobutadiene complex 1 (a
functionalized diol) was chosen as an initial target for synthesis.
This molecule contains a DMT protecting group and a phos-
phoramidite activating group, which make it conducive for
automated oligonucleotide synthesis. These functionalized hy-
droxyl groups will have similar reactivity as the nucleotides
used to synthesize oligonucleotides, making the target molecule
(1) compatible with the chemistry of the automated synthesizer.
It is readily recognized that any diol,17-20 after appropriate
functionalization, will meet the requirements for automated
synthesis.
Preparation of the cyclobutadiene complex (1, Scheme 1)
began with the Pd/Cu-catalyzed coupling21 of phenylacetylene
(2) with 4-bromophenethyl alcohol (3). Cyclization of the
resulting tolane (4) with cyclopentadienylcobaltdicarbonyl (Cp-
Co(CO)2) gave a mixture of isomers designated ortho and para
with regard to substitution around the cyclobutadiene ring. These
isomers were separated by chromotography.22 While the ortho
isomer (6) has the potential to form cycles when modified with
oligonucleotides, the para isomer (5) was protected to create
linear DNA structures. Monoprotected 7 was treated with
2-cyanoethyldiisopropylchlorophosphoramidite to give 1 after
isolation.23
Figure 1. Schematic illustration of a duplex oligonucleotide modified
organic (OMO).
A methoxy phenyleneethynylene trimer (8) was also synthe-
sized (Scheme 2). Pd/Cu-catalyzed coupling of 1,4-diiodo-2,5-
dimethoxybenzene (9) and 4-ethynylphenethyl alcohol (10)
results in phenyleneethynylene trimer 11, which was treated with
dimethoxytrityl chloride to give a mixture of diprotected,
monoprotected, and unprotected trimers. The desired monopro-
tected trimer 12 was isolated by flash chromatography and was
treated with 2-cyanoethyl diisopropylchlorophosphoramidite to
obtain 8.
Construction and Hybridization of a Cyclobutadiene
OMO for a Dimer Hybrid. We have recently described the
formation of an oligonucleotide-modified organometallic (OMO)
conjugate by attaching cyclobutadiene complex 1 to the 5′ end
of an oligonucleotide with a palindromic sequence of 5′
GTAGCGCTAC 3′. Thus, a dimer was formed upon annealing
(Figure 1).17 We now have applied the concepts of this simple
system to the more complex situation of having multiple
components.
(17) Waybright, S. M.; Singleton, C. P.; Tour, J. M.; Murphy, C. J.;
Bunz, U. H. F. Organometallics 2000, 19, 368.
(18) Kool, E. T.; Breslow, R. Angew. Chem., Int. Ed. Engl. 1992, 31,
1617.
Construction and Characterization of OMOs for Oligo-
meric and Polymeric Hybrids. To obtain polymeric and
oligomeric motifs, the cyclobutadiene complex 1 and the
methoxy-substituted phenyleneethynylene trimer 8 were modi-
fied with oligonuclotides on both sides rather than on only one
as previously described.17 The oligonucleotides are dodecamers
containing palindromic restriction sites to allow subsequent
enzymatic lysis of the duplex DNA. Fourteen random sequences
were designed, each containing a restriction site such that no
two sequences (or their complements) are similar.24 Thus when
mixed together, a single strand will pair only with its comple-
ment and not with some other undesired strand.
(19) (a) Thuong, N. T.; Chassignol, M. Tetrahedron Lett. 1988, 26, 5905.
(b) Durand, M.; Chevrie, K.; Chassignol, M.; Thuong, N. T.; Maurizot, J.
C. Nucleic Acids Res. 1990, 18, 6353. (c) Giovannangeli, C.; Montenay-
Garestier, T.; Rougee, M.; Chassignol, M.; Thuong, N. T.; Helene, C. J.
Am. Chem. Soc. 1991, 113, 7775.
(20) (a) Manikrao, S.; Wu, T.; Letsinger, R. L. J. Am. Chem. Soc. 1992,
114, 8768. (b) Letsinger, R. L.; Wu, T. J. Am. Chem. Soc. 1994, 116, 811.
(c) Letsinger, R. L.; Wu, T. J. Am. Chem. Soc. 1995, 117, 7323. (d) Lewis,
F. D.; Helvoigt, S. A.; Letsinger, R. L. J. Chem. Soc., Chem. Commun.
1999, 327.
(21) Zhang, Y.; Schuster, G. B. J. Org. Chem. 1997, 59, 11855.
(22) Given that the ortho isomer should have a greater dipole moment
than the para isomer, the faster running spot on TLC was assigned the
para isomer. This was confirmed with 13C NMR with the line width set at
zero. The spectra of the DMT-protected, phosphoramidite-activated forms
of each isomer were compared. There were four cyclobutadiene peaks
distinguishable for the ortho isomer and only three for the para isomer (Cs
symmetry).
(23) Coleman, R. S.; Kesicki, E. A. J. Am. Chem. Soc. 1994, 116, 11636.
(24) Seeman, N. C. J. Theor. Biol. 1982, 99, 237.

1830 J. Am. Chem. Soc., Vol. 123, No. 9, 2001
Waybright et al.
Figure 2. Schematic illustration of OMO constructs.
A series of oligonucleotides of the DNA-organic-DNA motif
were constructed (Figure 2). The OMOs were assembled as
follows: (1) The 12-base sequence was synthesized on an
automated synthesizer. (2) Cyclobutadiene complex 1 (blue balls
in Figure 2) or phenyleneethynylene trimer 8 (red balls) in THF
was added to the growing oligonucleotide. (3) A second 12-
base sequence was synthesized onto the strand.
Trityl cleavage data confirmed the addition of the organic
molecule (1 or 8) and the subsequent addition of the next
nucleotide. It was also noted that the solutions of oligonucle-
otides modified with cyclobutadiene (1) were yellowish in
colorsobviously due to the intrinsic color of the cyclobutadiene
complex. Concurrently, oligonucleotides modified with the
trimer (8) fluoresced when excited with long-wave UV light
from a hand-held lamp. In fact, this attribute became an efficient
way to verify the trityl data in the context of the desired OMO.
High-performance LC of the resulting OMOs revealed two
major peaks. The peak eluting at approximately 19 min
corresponded to DNA without an organic molecule attached.
The UV-vis spectrum of this component was characteristic of
DNA with a broad band at 260 nm. The peak eluting at
approximately 25 min was a result of the OMO whether the
organic was the cyclobutadiene complex (1) or the phenylene-
ethynylene trimer (8). The UV-vis spectrum of this peak
showed the characteristic DNA absorption at 260 nm and a
shoulder at 310 nm for the cyclobutadiene OMO case, and
absorptions at 318 and 375 nm for the trimer OMO case.
Figure 3 depicts the spectrum of the cyclobutadiene OMO
(OMO A, Figure 2)25 compared to the spectra of the oligo-
nucleotide control and the free cyclobutadiene complex (5).
Comparing the control spectrum with the cyclobutadiene OMO
spectrum, it is clear that the additional shoulder at 310 nm must
Figure 3. UV-vis spectra of DNA (A), cyclobutadiene OMO C (B),
and cyclobutadiene complex 5 (C). The dotted baselines are added for
clarity. Wavelength [nm]
be due to the organometallic complex as this feature is present
in the spectrum of 5. As a consequence of the differing solvent
conditions, the units of the y-axis are arbitrary. Regardless of
the solvent, the new features of the cyclobutadiene OMO must
be assigned to the covalent attachment of the cyclobutadiene
complex.
Figure 4 shows the spectrum of the trimer OMO (OMO G,
Figure 2) overlaid with spectra of free DNA and free trimer
(11; note that the trimer spectrum was taken in chloroform while
both DNA spectra were taken in water; thus, the units of the
y-axis are arbitrary). The UV-vis spectra of the trimer OMOs
show transitions at 318 and 375 nm that DNA alone does not
display, but are reflected in the spectra of the free trimer (11).
Enzymatic digestion of the OMOs to the corresponding
nucleosides also supported the incorporation of 1 or 8 into the
sugar-phosphate backbone. Utilizing a solvent gradient from 2%
acetonitrile to 70% acetonitrile in aqueous buffer resulted in
elution of 1 after 25 min and 8 after 31 min. Integrated areas of
the nucleoside peaks were consistent with the composition of
the corresponding OMOs (Table 1). Therefore, the cyclobuta-
(25) To aid the reader’s understanding, all organic molecules are
numbered with Arabic numerals (Schemes 1 and 2), all OMOs are indicated
with letters (Figure 2), and all self-assembled structures are labeled with
Roman numerals (Figure 7).

Oligonucleotide-Directed Assembly of Materials
J. Am. Chem. Soc., Vol. 123, No. 9, 2001 1831
concentrations of the OMO solutions must be known. Traditional
concentration analysis of oligonucleotides involves the absor-
bance of the 260 nm signature band of DNA and subsequent
calculation of the concentration from known extinction coef-
ficients. However, this method was not applicable as the organic
molecule (1 or 8) had a contribution to the 260 nm band of the
DNA resulting in skewed concentration results. Thus, a more
fundamental tool had to be employed. Phosphate analysis, in
which the total amount of inorganic phosphate in a sample was
measured allowed the correct OMO concentration to be
determined.
Our primary goal in this methodology was to obtain the OMO
concentration; our secondary goal was to establish a relationship
between the measured concentration via the traditional method
(absorption spectroscopy) and the actual concentration via the
phosphate analysis. Not surprisingly, when actual concentration
was plotted versus the measured concentration at 260 nm for
each organic, the relationship was linear (Figure 6). This
relationship allows us to avoid the time-consuming phosphate
analysis and utilize the data from the simpler 260-nm-absorbance
protocol. It should be noted that this entire exercise could have
been avoided by knowing the extinction coefficient of 1 or 8 at
260 nm. This measurement is trivial in organic solvents;
however, it is much less so in aqueous solvents in which the
OMOs are soluble but, of course, not 1 or 8.
Figure 4. UV-vis spectra of DNA (A), trimer OMO G (B), and trimer
11 (C). Wavelength [nm]
Table 1. Typical Enzyme Digestion Data for OMOsa
I (trimer)
P (cyclobutadiene)
OMO
base
ret.
time
actual
comp.
calcd
comp.
ret.
time
actual
comp.
calcd
comp.
C
G
T
A
3.55
6.46
8.27
14.38
30.77
5.9
5.2
8.4
4.5
6
5
8
5
3.57
6.47
8.16
14.36
25.83
1.2
8.9
6.5
7.4
2
9
6
7
Organic
a The retention times for nucleoside in minutes and organic peaks
are presented along with the integrated area of nucleoside peaks
compared to calculated composition of the OMO.
Hybridization of OMOs into Oligomeric and Polymeric
Hybrids. The OMOs in Figure 2 were annealed to form duplex
DNA resulting in hybrids (Table 2). By hybridizing OMOs E
and Q, or Q and R we can produce self-assembled polymers of
high molecular weight. Hybridizing OMOs E and Q will result
in polymer containing all cyclobutadiene OMOs while hybrid-
izing OMOs Q and R will lead to a polymer of alternating
cyclobutadiene and trimer OMOs. Oligomeric motifs can be
achieved similarly. These include the following: All trimer
OMO oligomers {G+H}, {G+H+I}, {G+H+I+J}, {G+
H+I+J+K}, {G+H+I+J+K+L}, and {G+H+I+J+K+
L+M}; all cyclobutadiene OMO oligomers {C+D}, {C+D+E},
and {C+D+E+F}; and mixed cyclobutadiene/trimer OMO
oligomers {F+G}, {C+D+R}, and {E+F+G+H}. The picto-
rial representations are given in Table 2.
Each hybrid shown in Table 2 was annealed from its
corresponding OMO monomers. Melting temperature studies
were performed on each hybrid. These data are presented in
Table 2. It was evident that oligonucleotide portions of each
OMO acted independently, that is, each 12-base segment
hybridizes independently of the other segments. Additionally,
it was observed that the longer oligomers (series I-VI) exhibited
sharper melting points (Figure 7). This is likely due to the
decreasing contribution of the dangling single-stranded ends with
longer oligomers.
Figure 5. Fluorescence excitation and emission spectra for trimer OMO
(G). Wavelength [nm]
diene complex (1) or the phenyleneethynylene trimer (8) must
have been included into the oligonucleotide strand as desired.
This is verified by UV-vis, enzyme digestion, qualitative visual
inspection, and, most convincingly, trityl cleavage data. These
data show cleavage of trityl groups from the nucleotides linked
to the growing oligonucleotide after the addition of 1 or 8san
observation that occurs only if 1 or 8 has been successfully
added.
Fluorescence measurements were performed on the trimer
OMOs (OMO G, see Figure 5). Excitations at 323, 370, and
388 nm resulted in a single emission at 410 nm. This observation
was consistent for all pheneyleneethynylene trimer OMOs. Both
the phenyleneethynylene trimer and the trimer OMOs have
quantum yields of near unity (0.95 to 1.0 at 370 nm excitation).26
Neither the cyclobutadiene modified nor the unmodified oli-
gonucleotides showed any fluorescence.
Fluorescence spectra were taken of the hybrids (I-VI,
X-XII) both before and after annealing. Quantum yields were
calculated by using quinine sulfate as a standard.26 The quantum
yields for I-VI were essentially unity (Table 2). However, for
hybrids X-XII, there was a noticeable decrease in quantum
yield. It is known that organometallic π-complexes efficiently
quench fluorescence;27 thus, this decrease is likely due to the
introduction of the cyclobutadiene complex.
A 12% native polyacrylamide analytical gel was run at 6 °C.
The gel clearly showed the annealed DNA strands when stained
with the intercalating dye ethidium bromide (Figure 8). To
determine the size of the OMO hybrids, a standard size marker
To ensure correct molar ratios of single-stranded OMOs in
the creation of the desired double-stranded structures, the exact
(26) Quinine sulfate was used as the standard and quantum yields were
determined as described in the following: Demas, J. N.; Crosby, G. A. J.
Phys. Chem. 1971, 75, 991.
(27) Steffen, W.; Bunz, U. H. F. Macromolecules 2000, 33, 9518.

1832 J. Am. Chem. Soc., Vol. 123, No. 9, 2001
Waybright et al.
Figure 6. Relationship of actual and measured concentration of cyclobutadiene OMOs (A-F, O-Q) and phenyleneethynylene trimers (G-N, R).
The actual concentration was determined by phosphate analysis; the measured concentration was determined by absorbance at 260 nm.
Table 2. Melting Temperature and Fluorescence Quantum Yields Compared to Quinine Sulfate for Annealed and Unannealed Oligomer and
Polymer Hybrids of Phenylenethynylene Trimer (red balls) and Cyclobutadiene Complex (blue balls) OMOsa
a Polymers are represented by XIII and XIV; XV is a DNA control
of a 25 base pair ladder in lane 6 was used. The PCR standards
show the 25, 50, 75, and 100 base pair fragments.
24 single bases for a total of 48 bases and migrates as a fragment
of approximately 50 base pairs in size. This trend is consistent
throughout all of the OMO hybrids.
In typical gel electrophoresis the DNA fragment migrates as
a function of the number of base pairs that it contains. The OMO
hybrids (I-VI) contain a portion of the DNA that anneals to
its complement and a portion at each end that does not have a
complement and thus remains single-stranded. The OMO
hybrids (I-VI) migrate through a native polyacrylamide gel
as a function of the total number of bases including double-
and single-stranded regions. This is evident when comparing
the control DNA in lane 1 to the size standards in lanes 5 and
6. Control XV (lane 1) contains 24 double-stranded bases and
Hybrid I (lane 5) has 36 bases and runs as a fragment of
approximately 35 base pairs when compared to the standards
in lane 6. Hybrid II (lane 4) has 48 bases and when compared
to standards in lane 6 runs slightly faster than the 50-base-pair
standard. Lane 3 contained hybrid III and clearly had a mobility
of a DNA fragment of 60 base pairs when compared to the
standards in lane 7. These hybrids can be compared with the
control hybrid XV (lane 1) that is 48 bases in size. Hybrid II

Oligonucleotide-Directed Assembly of Materials
J. Am. Chem. Soc., Vol. 123, No. 9, 2001 1833
sequence taking into account the addition of the organic moiety.
The organic molecule does not interfere with the ability of the
DNA to anneal. Hybrid VI in lane 2 does not show one discrete
band but several. The slowest moving migrates as a fragment
of approximately 110 base pair in size and a larger band at 75
bases when compared with the size standards in lane 6. Hybrid
VI is made by the annealing of 7 separate segments to produce
a heptamer that migrates as a 96 base fragment. Due to partial
annealing we see bands that correspond to 72 (pentamer) and
84 (hexamer) as well as the 96 (heptamer) base band. Also,
lane 3 containing hybrid III shows bands corresponding to 48
and 36 bases. Lane 4 has an additional band at 36 bases as
does lane 1 containing control XV. These additional bands are
expected if any slight deviation from precise stoichiometric ratio
occurs.
Figure 7. Melting temperature curves for dimer (I), trimer (II), and
heptamer (VI).
Conclusion
In conclusion, we have demonstrated that defined oligomeric
materials can be formed by hybridization of DNA-containing
organic modules. The concept is not restricted to the modules
utilized here, but should be extendable to any organic building
block containing hydroxy groups functionalized for automated
synthesis. Thus, when designing a self-assembled system, one
is not restricted to working with molecules that self-assemble
on their own, but rather, one can use any molecule having a
desirable property or function. This concept allows a general
approach to nano-construction where the structure is not
dependent on the modules used, rather it is dependent only on
the DNA used to link the modules together!
Figure 8. Polyacrylamide gel of four oligomeric hybrids. Lanes as
follows: 1, DNA control XV; 2, heptamer VI; 3, tetramer III; 4, trimer
II; 5, dimer I; and 6, 25 base pair PCR ladder.
Acknowledgment. The authors thank NSF-EPSCoR and
USC start-up for funding. K.W. is an REU participant from
UC Santa Cruz. U.H.F.B. is a recipient of the NSF CAREER
award (2000-2003) and a Dreyfus Teacher Scholar 2000-2005.
(lane 4) and the control hybrid XV (lane 1) have comparable
mobilities and therefore must be of similar size.
Supporting Information Available: Experimental and
spectroscopic details for 1-12, synthesis and purification of
OMOs A-R, phosphate analysis, melting curves, and PAGE
details (PDF). This material is available free of charge via the
Internet at http://pubs.acs.org.
A step pattern formed by the increase in size of the oligomer
hybrids is present when comparing lanes 3 (hybrid III of 60
bases), 4 (hybrid II of 48 bases), and 5 (hybrid I of 36 bases)
to lane 1 (control XV of 48 bases) and to the size standards in
lanes 6 and 7. The bands present in lanes 3, 4, and 5 correspond
to the size of the fragments expected when estimated by the
JA000950K