Dipeptide self-assembly

Figure 6 A (a) Schematic of the formation of tubular (single or multiwalled), spherical, or fihrillar structures via dipeptide self-assembly, (b) Proposed model for the formation of aligned peptide nanotube arrays. Scanning electron micrograph of (i) the vertically aligned peptide nanotubes, (ii) the nanotube arrays, and (iii) an individual nanotube obtained. Reprint with permission from Ref. [7].

Percec, V. et al. Principles of self-assembly of helical pores from dendritic dipeptides, Proc. Natl. Acad. Set USA., 103, 2518, 2006. 

Jayawama V, Ali M, Jowitt TA et al (2006) Nanostmctured hydrogels for three- dimensional cell culture through self-assembly of fluorenyhnethoxycarhonyl- dipeptides. Adv Mater 18 611-614... 

Liebmann T, Rydholm S, Akpe V et al (2007) Self-assembling fmoc dipeptide hydrogel for in situ 3d cell culturing. BMC Biotechnol 7 88... 

Mahler A, Reches M, Rechter M et al (2006) Rigid, self-assembled hydrogel composed of a modified aromatic dipeptide. Adv Mater 18 1365-1370... 

Dutt A, Drew MGB, Animesh P. /3-Sheet mediated self-assembly of dipeptides of w-amino acids and remarkable fibrillation in the solid state. Org Biomol Chem 2005 3 2250-2254. 

The primary peptide structure brings options for sequence tailoring that generate specific functionalities and self-assembly characteristics. Examples are amphiphilic dendritic dipeptides making helical pores (Percec, 2006) ... 

Percec, V. Amphiphilic Dendritic Dipeptides and Their Self-Assembly into Helical Pores, 2005-171494 2006088499 (2006). 

A range of functionalized and unfunctionalized self-assembling fibrous structures have been tested for their biocompatibility and ability to provide cells with a favorable micro- and nanoenvironments for soft tissue engineering. In this section, studies that focus on amyloid fibrils, on peptide amphi-philes, on ionic complementary peptides, and on dipeptide structures are reviewed. Hard tissue engineering, composites, and coating are also explored followed by macroscopic structures and networks that can be created from fibrous protein structures. 

Fig. 5 Visualization of the self-assemblies of PB25-i>-PE075 left cryogenic transmission electron micrograph) and of the corresponding dipeptide-grafted hybrid (right fluorescence micrograph) in water [27]...

Another system which directly forms porous columnar stmcmres is described by Percec and co-workers [72]. They reported that dipeplide moieties can be used to self-assemble in cone-shaped dendrons to form nanometer-sized hollow columns. The self-assembly is based on the H-bonds between the dipeptides. The porous columns were used as ion channels, for instance for proton transpKMt. 

The first dipeptide nanotube system was L-Val-L-Ala (VA), which forms crystals with narrow hydrophobic channels (diameter about 5 A) lined by peptide side chains.This structure is conceptually different from those of the cyclic peptides in that the pores are generated from self-assembly of small molecules, which are hydrogen bonded, head-to-tail, into helices (Fig. 3a). The extremely robust three-dimensional hydrogen-bonding scaffold was since observed for a series of other hydro-phobic dipeptides.Pore size can be regulated from 3.3 A (L-Ile-L-Val) to 5.2 A (L-Ala-L-Val) by adjusting the bulk of the hydrophobic side chains. Furthermore, L-Ala-L-Val has pores that can adapt their shapes and sizes to absorb large solvent molecules like 2-butanol. 

Peptide-based self-assembly is capable of synthesizing nanomaterials with various microstructures from tubes to spheres. Dipeptides, probably the simplest building blocks with a versatility in controlling microstructures, can form tubular, spherical, fibrous, or bundle, and array structures by modifying motifs on the dipeptides and/or altering synthesis conditions (Figure 6.4a). For example, the Alzheimer s p-amyloid peptide with diphenylalanine motif forms multiwaUed nanotubes when the peptide is... 

Preparation of cryogels [297] based on the self-assembled dipeptide molecules, study of rheological properties and macroporous morphology of resulting cryogels... 

Hydrogen-bonds also participate in the self-assembly of organotin derivatives of dipeptides, e.g. (L-methionyl-L-methioninato)dimethyltin and (L-alanyl-L-histidinato)dimethyltin [79], in the hydantoie acid derivative of triphenyltin, Ph3Sn(OOCCH2NHCONH2) [80], and in (4-benzoylpyrazol-5-onato)tributyltin [81]. 

Villa A, Peter C, van der Vegt NFA (2009) Self-assembling dipeptides conformational sampling in solvent-free coarse-grained simulation. Phys Chem Chem Phys 11 2077-2086... 

However, there can be limits to this approach because it is not always clear whether the chosen CG mapping scheme can converge to an optimal fit. For liquid mixtures or solutions, the situation is more complex because several RDFs that mutually affect each other need to be simultaneously reproduced. In additicni, for dilute solutions, where we have a low concentration of solute, the solute-solute RDFs converge very slowly in the CG simulations. In this case, the PMF between the solute molecules can be obtained using free-energy calculation methods such as umbrella sampling or constraint dynamics. Recently, these methods have been used in an iterative optimization approach to study self-assembling dipeptides at the CG scale [75, 76]. The PMF between solute molecules in a solvent box, Fpi (r), is calculated by all-atom simulation from n distance constraint simulations ... 

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