Change in Sheet Structure upon Adsorption

In the group of Boden, the self-assembly of a peptide called P11-2, i.e. has been studied both in solution and adsorbed on mica substrates 33-35 . In solution, at very low concentrations (< 0.05 mM) the peptide was present as random coil, as confirmed by CD spectroscopy. At slightly higher concentrations ( 0.07 mM) b-sheet ribbons start to emerge and at even higher concentrations (> 0.6 mM) rigid fibrils and fibers have been observed by electron microscopy (Fig. 13.15) 33 . The observed...

Contents

List of Contributors XIX Part 1 Structure Foldamer Design Concepts 1 1 Foldamers Based on Local Conformational Preferences 3 1.3.1 Local Conformational Control 6 1.3.2 Folded Conformations of p-conjugated Systems 9 1.3.2.1 Crescents and Helices 9 1.3.3 Partially p-conjugated Oligomers 16 1.4.1 Tertiary Aromatic Amides, Imides and Ureas 18 1.4.2 Tertiary Aliphatic Amides Polyprolines and Peptoids 20 1.4.3 Hindered Polymer and Oligomer Backbones 23 1.5 Conformational Transitions 25 1.6 Conclusion...

Design Considerations

When designing a foldamer sequence to adopt a specific conformation at the interface, ''positive'' and ''negative'' design approaches, leading to rational stabilization and destabilization of local geometries by introduction of attractive and repulsive interactions, have to be combined in order to realize the ''minimally frustrated'' state 5 . One first important aspect concerns the use of hetero-sequences to bias conformational preferences in foldamers. For example, from Fig. 13.4 Pathway...

Foldamers Stabilized by Adjacent Donoracceptor Aromatic Units

One way of enhancing the selectivity in aromatic-aromatic interactions is to polarize the aromatic systems and make one unit rich in electron density and the other deficient. With two different kinds of monomer units in a linear oligomer, different folding motifs may be obtained from the sequence of the monomer units 98 . This highly efficient strategy was pioneered by Iverson and colleagues and the class of foldamers is called aedamers (aromatic electron donor-acceptor oligomers) 99 ....

Foldamers Stabilized by Adjacent Identical Aromatic Units

From the viewpoint of geometrical manipulation, it is not a good idea to start designing solvophobic foldamers from flexible aliphatic hydrocarbon chains. Instead, rigid aromatic rings represent much more reasonable solvophobes with higher levels of geometrical constraints - effective aromatic interactions are only obtained in three main geometries edge-face, offset stacked, and stacked 7578 . For aromatic foldamers, geometrical manipulation is achieved through both the aromatic units and the...

Folding in Solution and at Interfaces

In solution, foldamers adopt preferred secondary structures that almost exclusively consist of various helix or sheet types. In biomacromolecules, such as proteins, these secondary structural motifs can further be organized into higher order structures using covalent loops, i.e. tertiary structures, and even further using noncovalent interactions between subunits, i.e. quaternary structures. At interfaces, however, both the conformational preference of the foldamer and the intermolecular...

H

Fig. 1.17 Transitions between helical and extended linear conformations via sequential protonation and deprotonation. shown in Chapter 10, nucleic acids have proven particularly useful in this respect. The foldamers described in this chapter have also been much exploited, particularly the ''fully predictable'' foldamers presented in Section 1.3. Leaving aside the simplest transitions such as, for example, the dynamic equilibrium between right-handed and left-handed helical conformations, which...

Helically Folding Polymers

Eiji Yashima and Katsuhiro Maeda 11.1 Macromolecular helicity is one of the most important and basic structural motifs that can often be seen in naturally occurring biological polymers, such as proteins and nucleic acids. They are optically active and fold into a one-handed helical conformation which directs their sophisticated and fundamental functions in living systems. Therefore, in polymer and supramolecular chemistry, the design and synthesis of polymers and oligomers that fold into a...

Info

Folding, as it occurs in biopolymers, refers to the prevalence of well-defined con-formers in solution and, in most cases, to proximity in the folded state between chemical groups that are remote in the molecules' backbones. As illustrated in the first three chapters of this book, a multitude of non-natural folding oligomeric molecules - termed foldamers - have been designed, prepared and characterized 1-3 . The factors that promote folding of a linear molecular strand are manifold specific...

Introduction

A foldamer 1 can be defined as a (macro)molecular strand that is capable of adopting a well-defined, thermodynamically favored conformation in solution 2 . In order to provide a broader description that can be extended to interfaces as well, we view the foldamer's conformational preference as being the result of the action of internal and external boundary conditions, which involve various types of interactions (Fig. 13.1). In solution in the isolated single foldamer molecule, only internal...

Knowledge for Generations

Each generation has its unique needs and aspirations. When Charles Wiley first opened his small printing shop in lower Manhattan in 1807, it was a generation of boundless potential searching for an identity. And we were there, helping to define a new American literary tradition. Over half a century later, in the midst of the Second Industrial Revolution, it was a generation focused on building the future. Once again, we were there, supplying the critical scientific, technical, and engineering...

O

Fig. 8.5 Terphenyl and terephthalamide scaffolds and Bcl-xL inhibiting derivatives. Fig. 8.5 Terphenyl and terephthalamide scaffolds and Bcl-xL inhibiting derivatives. spatial arrangement of substituted i, i + 4 and i + 7 positions of short a-helical segments 142 . Therefore, the terphenyl scaffold has been utilized to target helix recognizing proteins 142-146 . The terphenyl ring systems have been synthesized using Suzuki 143, 144 or Negishi 142 couplings. Low water solubility of terphenyl...

P

Previously, Millich had found that acid-coated glass can act as a catalyst for the polymerization of isocyanides, although not very efficiently 33, 46 . Metselaar et al. recently reported that the acid (TFA)-initiated polymerization of isocya-nopeptides leads to extremely long polymers with lengths up to 14 mm (Fig. 12.10D) 85, 90 . For the polymerization of 35a at a TFA concentration of 1 mM, kinetic studies revealed a large entropy of activation ( 170 J mol 1 K_1), which indicates a very high...

Protein Design

Jean-LucJestin and Frederic Pecorari 9.1 Most natural proteins are not adapted to our needs for therapeutic or even bio-technological uses. The challenge of protein design is to define efficient and comprehensive ways for the identification of new or improved proteins with the required properties. The design of new proteins relies on sequence-structure-function relationships and is limited by our partial knowledge of the protein folding mechanism. But as we will see in this chapter, creating...

RHN Jn HacHJI 5 J 3 L V

Fig. 1.8 Examples of aliphatic oligomers, the conformations of which are defined by interactions between adjacent units. The 3,5-linked polypyrrolin-4-one scaffold (Fig. 1.8a) allows for a wide variety of folding motifs. This outcome may be ascribed to the cooperative effect of (i) the dihedral angles of the backbone that are locked by the pyrrolinone ring, (ii) restricted rotations due to gauche steric interactions between the side chains and the neighboring pyrrolinone rings, and (iii) C...

S03

Fig. 8.14 Major repeat of heparin and a heparin binding aryl amide. Backbone rigidifying H-bonds are shown as dashed lines. inhibitory effect on cholesterol uptake in either model. On the other hand, while none of the previously tested a-peptide inhibitors induced effects in whole CaCO-2 cells, a b-peptide nonamer decreased the absorption rate of radiolabeled cholesterol to background levels (indicated by an increase in T1 2 of cholesterol absorption rate from 102 min to 2.6 h). This suggested...

Helical Structures Formed upon Adsorption

Tween Detergent

Adsorption of unfolded structures at interfaces can also induce the formation of helical conformations. Hydrophobins are among the best biosurfactants and Fig. 13.9 Self-assembly and conformational equilibria of hydrophobin SC3 in different environments and at different interfaces (Tween detergent poly(ethylene glycol) sorbitan monolaurate with n 20) 22 . (Adapted from ref. 22 .) Fig. 13.9 Self-assembly and conformational equilibria of hydrophobin SC3 in different environments and at different...

Foldamers Based on Solvophobic Effects

Solvophobic effects are responsible for the association of poorly-solvated molecular surfaces and are one of the most important noncovalent forces used by nature in biofoldamers. Unlike specific interactions such as hydrogen bonds, solvophobic effects rely on collective interactions among solvents and solutes instead of specific functional groups for operation. To use solvophobic effects for foldamer design, one must create solvophobic sites or patches along the primary sequence to collapse an...

Adsorbed Sheet Structures at Interfaces

Another important class of secondary structures is the sheet motif. b-Sheet structures are abundant peptide and protein secondary structures, and similar secondary sheet structures are also found in a variety of artificial backbones (see Chapter 4). In most sheet structures, the individual foldamer chains are stretched and intermolecular interactions between different strands lead to the formation of two-dimensional ribbons or sheets via dimerization and further aggregation. A few examples of...

Mvs2

Fig. 12.12 Schematic representation of the three univalent and the two mixed valence redox states of polymer 56 and the colors of the corresponding polymer solutions. (Adapted with permission from Ref. 114 Copyright 2005, Wiley-VCH.) distinguishable chiroptical properties as was shown by CD spectroscopy measurements and therefore can act as a multistate redox-switchable organic system. One of the early examples of polyisocyanides bearing electron acceptor and donor groups was reported by...

Inversion of Macromolecular Helicity

Right Handed Helix

Another interesting and unique feature of dynamic helical polymers is the reversible helix inversion helix-helix PM transition between right- and left-handed helical conformations regulated by external stimuli, such as a change in temperature, solvent or by irradiation with light. Because the extremely high sensitivity of dynamic helices to a chiral environment arising from a high cooperativity, the formation of an excess of the preferred helical sense can be altered, resulting in the inversion...