Peptide-Based Structures

Lynn, D., Conticello, V., Morgan, D.A., and Dong, J. Self-Assembling-Beta-Amyloid Peptide-Based Structures and Control of Their Self-Assembly by Changes in Metal Ions Concentration and Other Environmental Parameters, 2003-US9229 2003082900 (2003). 

General Design Concepts for Peptide-Based Structural Materials... 

Besides serving as structural building blocks to provide mechanical strength, peptide-based structures offer numerous possibilities to create novel bioactive and dynamic materials [57]. For instance, peptide sequences that facilitate mineralization and foster cell adhesion can be readily incorporated... 

To be successful in these applications, it is important that materials can self-assemble into precisely defined structures. Peptide-based polymers have many advantages over conventional synthetic polymers since they are able to hierarchically assemble into stable, ordered conformations [4]. Depending on the substituents of the amino acid side chain, polypeptides are able to adopt a multitude of... 

The way that Pn peptides self-assemble is important for polypeptides and proteins amyloid-type structures are believed to have the same core stmcture, and in fact the propensity to self-assemble in this manner is hypothesized to be a general property of polypeptides [52]. It is therefore unsurprising that systems featuring this motif are common. In recent years, a push towards the use of peptide-based self-assembled materials has led to increasing interest in extending their functionality by derivatising them. 

These are exciting times for peptide based materials. The number of investigators in this field and consequently the number of publications in this area have increased tremendously in recent years. Not since the middle of the past century has there been so much activity focused on the physical properties of peptidic materials. Then, efforts were focused on determination of the fundamental elements that make up protein structures, leading to the discoveries of the a—helix and the (3-sheet. Many years of study followed where the propensities of individual and combinations of amino acids to adopt and stabilize these structures were investigated. Now, this knowledge is being applied to the preparation, assembly, and use of peptide based materials with designed sequences. This volume summarizes recent developments in all these areas. 

Wakselman, M. Mazaleyrat, J.-P. Lin, R. C. Xie, J. Vigier, B. Vilain, A. C. Fesquet, S. Boggetto, N. Reboud-Ravaux, M. Design, synthesis and study of a selective cyclopeptidic mechanism-based inhibitor of human thrombin. In Peptides Chemistry, Structure... 

Van Regenmortel, M. H. V. (1999c), Molecular design versus empirical discovery in peptide-based vaccines. Coming to terms with fuzzy recognition sites and ill-defined structure-function relationships in immunology , Vaccine, 18, 216-221. 

Jeong and coworkers have reported peptide-based thermo-gelling systems using PEG-b-polyAla as an injectable cellular scaffold [315]. The polymer aqueous solution undergoes sol-gel transition as temperature increases. The fraction of the p-sheet structure of the poly Ala dictated the population and thickness of fibrous nanostructure in the hydrogel, which affected the proliferation and protein... 

For the orientation-based structure analysis of MAPs, uniformly oriented lipid bilayers are typically prepared on solid supports as illustrated in Fig. 2 [23, 47, 55]. These mechanically oriented membranes are advantageous for static ssNMR experiments, as they provide a robust way to orient a sample with any desired lipid composition, peptide concentration, and at any desired temperature. The lipids... 

The rational synthesis of peptide-based nanotubes by self-assembling of polypeptides into a supramolecular structure was demonstrated. This self-organization leads to peptide nanotubes, having channels of 0.8 nm in diameter and a few hundred nanometer long (68). The connectivity of the proteins in these nanotubes is provided by weak bonds, like hydrogen bonds. These structures benefit from the relative flexibility of the protein backbone, which does not exist in nanotubes of covalently bonded inorganic compounds. 

Inhibitors of human neutrophil collagenase and human stromelysin have been designed (577) which are based on previous classes of MMP inhibitors, iV-carboxyalkyl peptides (578, 579), and peptide-based hy-droxamic acids (117) (580, 581). The -CH3 and 2-phenylethyl groups are important for inhibition of MMP-3. The X-ray crystal structure of MMP-3 with bound 117 shows that the inhibitor chelates Zn(II)... 

A different kind of host consisting of a peptide-based bicyclic structure has been described.118 In this case, the chemical shifts changes were followed by HSQC spectra in deuterated acetic acid and in water, when titrated with cellobiose. In any case, a low but measurable binding affinity constant was found. 

Nilsson et al. designed an experiment to test the ability of a polymer to directly detect conformational changes within peptide/protein structure [27]. Using the zwitterionic polythiophene derivative, POWT, they succeeded in detecting the distinct conformations of synthetic peptides. The mechanism was concluded to be based on the polymer side chains charged interactions and hydrogen bonding with the proteins. 

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