Peptide-scaffold hybrids

The sigmatropic rearrangement products 10 and 12 and some of the intermediates shown in the previous figures have been used in the synthesis of peptide-scaffold hybrids. 

With the objective to improve the transport and the peptidase resistance of peptides, we have been engaged in the synthesis of the peptide-scaffold hybrids. In the course of our longstanding interest on these molecules, we have prepared a panoply of 

FIGURE 14 4 Generic structures of several peptide-scaffold hybrids prepared in our group. 

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REARRANGEMENTS IN CARBOHYDRATE TEMPLATES TO THE WAY TO PEPTIDE-SCAFFOLD HYBRIDS AND FUNCTIONALIZED HETEROCYCLES... 

This last class of peptide-scaffold hybrids (Q) is readily synthesized from the Claisen and Overman rearrangements products. Some examples of peptide-carbohydrate hybrids are shown in Figure 14.5. 

Our group has been interested in the synthesis of alkaloids [67] and related compounds [68,69]. In connection with our research on peptide-scaffold hybrids (see Section 14.3), we have synthesized a variety of partially reduced aromatic heterocyles [70-73]. As a step further, we have recently developed a methodology based in the sequential transformations of azide-alkene containing an electrophilic center, which is initiated by a 1,3-dipolar cycloaddition, followed by nitrogen extrusion, and latter transformation to an enamine that, in turn, reacts as nucleophile with the electrophile present in the molecule (Figure 14.6). 

Chapter 14, by Herraddn and coworkers, describes rearrangements of carbohydrate templates as the pathway to functionalized heterocycles and peptide-scaffold hybrids. 

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. 

C.T. Walsh, R.V.O. Brien, C. Khosla, Nonproteinogenic amino acid building blocks for non-ribosomal peptide and hybrid polyketide scaffolds. Angew. Chem. Int. Ed. 52, 7098-7124 (2013)... 

Hossain et al. [28,29] prepared CD peptide hybrids 21-22, in which pyrene (electron donor) and nitrobenzene (electron acceptor) were placed at both sides of CD on the peptide scaffold (Fig. 9). In an aqueous environment and in the absence of guests, the nitrobenzene moiety is located in the CD cavity, bringing it close to the pyrene moiety. Under these conditions the monomer emission of pyrene is effectively quenched by nitrobenzene. The fluorescence intensity dramatically increases with increasing concentration of a guest (e.g. lithocholic acid). The guest-responsive enhancement in the fluorescence intensity of 21 or 22 can be explained in terms of increased distance between the pyrene and nitrobenzene moieties, which is caused by exclusion of the nitrobenzene moiety from the CD cavity by guest accommodation. 

Smith, A.B. Jill, Savinov, S.N., Manjappara, U.V. and Chaiken, I.M. (2002) Peptide-small molecule hybrids via orthogonal deprotection-chemoselective conjugation to cysteine-anchored scaffolds. A model study. Organic Letters, 4, 4041—4044. 

Polymers tiiat can guide development of tissue through the addition of arginine-glycine-aspartic acid (RGD) or otirer polypeptide sequences have also been fabricated. The RGD sequence of amino acids is foimd in proteins of the extracellular matrix such as fibronectin, and one of the sequence s roles is to promote cell adhesion. The purpose of synthesizing such polymers is to manipulate the body into treating the syntiretic material, which mimics the extracellular matrix, like natural tissue. If successful, cells should then readily attach and proliferate on the scaffold. Shakesheff and co-workers provide a review of the three major techniques used to create polymer-peptide hybrid materials. ... 

Hosseinkhani H, Hosseinkhani M, Tian F, Kobayashi H, Tabata Y. Bone regeneration on a collagen sponge self-assembled peptide-amphiphile nanofiber hybrid scaffold. Tissue Eng 2007 13 11-9. 

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