Scaffold Template

The remainder of Section 14 deals with triple helices and collagen mimetic structures (Sections 14.2.3.1 and 14.2.4). A description of routes is included which covers the synthesis of triple-helical structures using template (scaffolds) from a Lys-Lys dimer (Section 14.2.4.1), Glu-Glu dimer (Section 14.2.4.2), and appropriate Cys-Cys branches (Section 14.2.4.3). The syntheses were carried out using solid-phase techniques. A scaffold (template) using the Kemp triacid is also presented (Section 14.2.4.4). Lastly, a chemoselective ligation is presented which joins appropriately defined reaction sites (Section 14.2.4.5).[23]... 

Instead of single porogen particles, bulk polymer scaffold templates (e.g., made from PLGA) can be utilized for the production of macroporous hydrogels. Therefore, the hydrogel precursor solution is cast and cured around the scaffold. After degradation of the polymer scaffold with a suitable chemical, a porous hydrogel matrix is left behind. 

In another paper, the same authors investigated the 1,3-dipolar cycloaddition on 2-(lH)-pyrazine scaffolds 72 and electron-rich azides, using Cu(0) and CUSO4 as pre-catalysts. To demonstrate the versatility of this approach, they reported the generation of different templates (73 in Scheme 25) as an application of cUck chemistry . They also investigated the Diels-Alder reaction of the so obtained triazoles with dimethyl acetylenedicarboxylate (DMAD), under microwave irradiation. The latter reaction allowed obtaining various pyridinones in good yields (74 and 75 in Scheme 25) [57]. 

The use of DNA hybridization just described opens up a novel, uncomplicated, yet powerful strategy for supramolecular synthesis Many different devices are connected to a distinct sequence codon and are subsequently organized on a suitable template strand. The utilization of appropriate nucleic acid scaffolds should even allow the fabrication of highly complex supramolecular structures by means of a modular construction kit. For approximately 20 years, the work of Seeman and coworkers [8,27] have been engaged in the rational construction of ID, 2D, and 3D DNA frameworks. They use branched DNA... 

Streptavidin-single-stranded DNA covalent conjugates were described as the building blocks for assembling nanostructured scaffolds [31], The amount and type of biotinylated ligands were used to modulate the affinity of duplex formation between solid-phase-bound nucleic acid templates and DNA-streptavidin conjugates. This system has been proposed for the design of fine-tuned sequence detection systems. 

Fig. 1.7 Schematic diagram to show the process involved in screening and crystallographic confirmation of scaffold or template libraries.

In the patent literature, Aventis has published a patent application covering hydroxamic acid containing macrocycles (39) with the same general template as the A-formyl-A-hydroxylamine macrocycles described above [114] and GlaxoSmithKline has published an application on macrocyclic PDF inhibitors containing a hydrazide scaffold (40) [115], No data has been published on these inhibitors to date. 

Recent patent disclosures reveal efforts to optimize within this template. The amide moiety has been cyclized to give dihydroisoquinolone inhibitors such as 9 and 10 [57]. Using various mono- and bicyclic core structure scaffolds, the amide has also been constrained in isoquinolone,... 

Wu and Sun have presented a versatile procedure for the liquid-phase synthesis of 1,2, ,4-tctrahydro-/i-carbolines [77]. After successful esterification of the MeO-PEG-OH utilized with Fmoc-protected tryptophan, one-pot cyclocondensations with various ketones and aldehydes were performed under microwave irradiation (Scheme 7.68). The desired products were released from the soluble support in good yields and high purity. The interest in this particular scaffold is due to the fact that the l,2,3,4-tetrahydro-/f-carboline pharmacophore is known to be an important structural element in several natural alkaloids, and that the template possesses multiple sites for combinatorial modifications. The microwave-assisted liquid-phase protocol furnished purer products than homogeneous protocols and product isolation/ purification was certainly simplified. 

Scheme 10. Scaffolding the interaction-mediating sidechains on cyclic hydrophobic core templates... 

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