Adamantane - peptides

In this instance, adamantane was present to promote interaction of peptides through its hydrophobicity, but its attachment did not hinder fibril formation. It might be possible to chemically or biologically derivatise this group before being introduced to the peptide, or to select another hydrophobic component that could be suitably modified and attached to the peptide. This research also highlights the feasibility of creating peptide arrays comprised of several different sequences. 

Attaching some short peptidic sequences to adamantane makes it possible to design novel antagonists. The bradykinin antagonist, which is used as an anticancer agent, is an example. The adamantane-based peptidic bradykinin analog was utilized in strucmre-activity relationship (SAR) studies on the bradykinin receptors and showed a potent activity in inhibition of bradykinin-induced cytokine release and stimulation of histamine release [142]. 

A unique feature of such DNA-directed self-assemblies is their site-selective immobilization, which makes it possible to construct well-defined nanostructures. On the other hand, the possibility of the introduction of a vast number of substitutes (like peptidic sequences, nucleoproteins, of hydrophobic hydrocarbon chains) to an adamantane core (adamantyl) makes such a process capable of designing steric colloidal and supramolecular conformations by setting hydrophobic/hydrophilic and other interactions. In addition, the rigidity of the adamantane structure can provide strength and rigidity to such self-assemblies [150]. 

Figure 27 Adamantane nucleus with amino acid substituents creates a peptidic matrix [151], The represented structure is Glu4-Glu2-Glu-[ADM]-Glu-Glu2-Glu4.

Bifunctional adamantyl, as a hydrophobic central core, can be used to construct peptidic scaffolding [151], as shown in Fig. 27. This is the reason why adamantane is considered one of the best MBBs. This may be considered an effective and practical strategy to substitute different amino acids or DNA segments on the adamantane core (Fig. 28). In other words, one may exploit nucleic acid (DNA or RNA) sequences as linkers and DNA hybridization (DNA probe) to attach to these modules with an adamantane core. Thus a DNA-adamantane-amino acid nanostructure may be produced. 

Figure 32 Adamantane-containing norbornene ( i )-constrained cyclic peptides possess the ability to transport ions across the model membranes in both specific and nonspecific ways [162].

Adamantane can be used to construct peptidic scaffolding and synthesis of artificial proteins. It has been introduced into different types of synthetic peptidic macrocycles, which are useful tools in peptide chemistry and stereochemistry studies and have many other applications as well. Introduction of amino acid-functionalized adamantane to the DNA nanostmctures might lead to construction of DNA-adamantane-amino acid nanostmctures with desirable stiffness and integrity. Diamondoids can be employed to constmct molecular rods, cages, and containers and also for utilization in different methods of self-assembly. In fact, through the development of self-assembly approaches and utilization of diamondoids in these processes, it would be possible to design and constmct novel nanostmctures for effective and specific carriers for each dmg. 

Another report showed that cyclodextrin vesicles (CDVs) (Section 5.3) can be decorated with peptides functionalized with an adamantane anchor. It was found that a (LeuGlu)4 octapeptide can induce a pH-dependent shape transformation of the vesicles at pH 7.4, the peptide merely binds to the vesicle surface, whereas at pH 5.0 it forms a jS-sheet and transforms the vesicles into a nanotube (Figure 7). It was shown that the vesicles release their contents as a result of this shape transformation. It should be emphasized that the pH range of this shape transformation matches the decrease in pH that occurs upon endosomal uptake by cells. Hence, these experiments suggest that the peptide-decorated CDVs may be a useful vehicle for intracellular delivery of drugs or antigens that are encapsulated inside the vesicle or bound on the surface of the vesicle. 

Figure 7 Molecular structures of amphiphilic S-cyclodextrin derivative 1, which self-assembles into CDVs, and adamantane-modilied octapeptide 2, which binds to the CDVs by host-guest interaction. Peptide 2 adapts a random coil conformation at pH 7.4 while bound to the vesicles. Upon acidification to pH 5.0, peptide 2 forms a S-sheet which induces a morphological change from a vesicle to a nanotube, with concomitant release of contents.

A second example from the Kros lab is particularly interesting, as it uses a nonpeptidic scaffold to template the formation of j6-structured peptides. A )8-cyclodextrin vesicle (CDV) is employed as a scaffold to template the assembly of an octapeptide, (LE)4, that is A-terminally modified with adamantane. The adamantane moiety forms an inclusion complex on the surface of the vesicles. The group uses CD spectroscopy to show that the peptide is unstructured... 

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