Chemistry Reference
In-Depth Information
11 together existed as a heterodimer and 12 as a homodimer. The ESI spectrum of the
1:1 mixture of 10 and 11 detected the doubly charged [10
þ
11
þ
2Cl]
22
(m/z ¼
1454.3) as the most abundant ion. For 12,[12
þ
12
þ
Cl]
2
(m/z ¼ 2636.3), corre-
sponding to the self-dimer 12†12, and [12
þ
Cl]
2
(m/z ¼ 1335.6), corresponding
to single strand 12, were the two major ions detected by electrospray ionization.
To account for the formation of dimers by 10 and 11, and 12 itself, the best expla-
nation is that, instead of being extended, strands 10 and 11 and strand 12 adopt folded
conformations when associated into their corresponding H bonded assemblies. The
specific (and most reasonable) model involves the folded (stacked) conformations
as shown in Figure 9.8a adopted by strands 10 and 11. Based on the same analysis,
the molecules of 12 can associate into a homodimer only by adopting a similar folded
conformation (Fig. 9.8b). This model of self-assembling foldamers is fully consistent
with the above experimental results. Thus, these molecular duplexes have the novel
feature of combining sequence-specific self-assembly and the folding of component
strands. It is not yet clear whether the folded conformations are contingent upon the
association of the two strands by forming, for example, the first four H bonds, or
vice versa. Further study on this system should lead to new self-assembling and
folding structures.
9.7. DIRECTED ASSEMBLY: FORMATION OF
b
-SHEETS AND
SUPRAMOLECULAR BLOCK COPOLYMERS
9.7.1. Directed Assembly: Templated Formation
of Two-Stranded
b
-Sheets
When tethered to structural units that may associate in more than one way, an H
bonded duplex template will help specify the intermolecular interaction, leading to
a single assembly. The possibility of directing the association of natural peptide
strands was tested by using our H bonded duplexes as templates.
Because the interstrand distance of a duplex, based on the crystal structures of 4-H
bonded duplexes (Gong et al. 1999), is the same as that (
5
˚
)inab-sheet, these
hydrogen bonded duplexes may serve as specific, noncovalent templates for directing
and nucleating b-sheet structures when attached to natural oligopeptide strands.
Because the H bonding sequence of the duplex template can be designed to be unsym-
metrical, two flexible peptide chains can be bought into proximity and thus forced to
pair with each other, leading to a double-stranded, antiparallel b-sheet (Fig. 9.9).
Our results confirmed the feasibility of this strategy (Zeng et al. 2002). Peptide
segments were attached to an unsymmetrical, 4-H bonded heteroduplex template
with the complementary sequences of ADAA/DADD, leading to four hybrid
strands 13a, 13b, 14a, and 14b. Combination of strands 13a and 13b with strands
14a and 14b resulted in four different pairs. The formation of well-defined
b-sheets by different combinations of paired peptide sequences was confirmed
by 1-D and 2-D NMR, ITC, and VPO studies. For example, 2-D NMR (NOESY)
showed interstrand NOEs corresponding to protons of duplex templates and the
