Sequencing synthetic, creation

Certain types of molecules, especially polypeptides and polynucleotides, lend themselves to synthesis on solid supports. In such syntheses, the starting material is attached to a small particle (bead) or a surface and the molecule remains attached during the course of the synthetic sequence. Solid phase synthesis also plays a key role in creation of combinatorial libraries, that is, collections of many molecules synthesized by a sequence of reactions in which the subunits are systematically varied to create a range of structures (molecular diversity). 

Synthetic haptens mimicking some critical epitopic structures on larger macromolecules are often conjugated to carriers to create an immune response to the larger parent molecule. For instance, short peptide segments can be synthesized from the known sequence of a viral coat protein and coupled to a carrier to induce immunogenicity toward the native virus. This type of synthetic approach to immunogen production has become the basis of much of the current research into the creation of vaccines. 

When discussing various methods for the synthesis of protein-like HP-copolymers from the monomeric precursors (Sect. 2.1), we pointed to the possibility of implementation of both polymerization and polycondensation processes. The studies of the potentials of the latter approach in the creation of protein-like macromolecular systems have already been started. The first published results show that using true selected reactions of the polycondensation type and appropriate synthetic conditions (structure and reactivity of comonomers, solvent, temperature, reagent concentration and comonomer ratio, the order of the reagents introduction into the feed, etc.) one has a chance to produce the polymer chains with a desirable set of monomer sequences. 

This synthetic sequence encompasses not only protecting-group operations, but also the creation of an acid function, and this requires a particular order for the steps. 

These principles are best recognized when studying relatively simple molecular systems that have an ability to exploit weak interactions to create structure. Among many, peptides are the perfect choice for such studies considering their versatility in make up given the 20+ natural and synthetic amino acid residues, and their functional diversity. In addition, the amino acid sequence of the primary structure combined with the ability of forming secondary (3-sheet or a-helix structures provide substantial room for the creation of hierarchical structures based on weak intermolecular forces, mainly hydrogen bonds. A limited sequence of residues also prevents additional complication from tertiary and quaternary structures as seen with proteins. 

Cyclopropane ring scission occurs readily either under reducing conditions or upon the action of electrophilic or nucleophilic agents. These possibilities offer multiple options for the synthetic utilization of the cyclopropane moiety in organic synthesis. One of the most important applications is based upon the use of the cyclopropanation-catalytic hydrogenation sequence as a method for the creation of the gem-dimethyl moiety, a fragment frequently encountered in many naturally occurring compounds. A typical example is shown in Scheme 2.161. 

New synthetic methods should be designed in concert with new concepts of modem chemistry. These key concepts involve atom and step economies and the use of highly efficient catalytic reactions. The hydroformylation reaction follows these guidelines. It requires a low catalyst loading, allows the creation of three new chemical bonds, and introduces a highly reactive aldehyde. We have already demonstrated that its combination with other chemical reactions in well-developed domino sequences shows its potential in the synthesis of complex molecules. The few previously synthesized natural molecules demonstrated that the robustness of the catalyst system and other domino reactions are possible to create even more complexity and diversity. 

Genetically directed synthesis has also been employed for the creation of a series of elastin-mimetic (BAB)-type triblock copolymers. ° The identity of the elastin-mimetic blocks within this macromolecular architecture could be varied between the elastomeric and plastic sequences to provide a versatile and controllable mechanical response within the synthetic constmct. The hydrophobic endblocks (B) were derived from the plastic repeat sequence [(Val/Ile)-Pro-Ala-Val-Gly]. In contrast, the hydrophilic midblock (A) was based on the elastomeric repeat sequence [(Val-Pro-Gly-Yaa-Gly)] in which polar glutamic acid residues are introduced at the Yaa position periodically throughout the repetitive sequence. These materials undergo reversible, temperature-dependent phase segregation of the hydrophobic endblock from aqueous... 

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