Synthesis of Polypeptides

Polypeptides can be synthesized by different methods. Solid phase synthesis is the most versatile method regarding the control of the polypeptide sequence and 

Several methods have been developed to overcome these problems. Schlaad and coworkers reduced the activity of the end group by employing ammonium salts in which the amine is present in the equilibrium only to a minor extent. Furthermore, 

The low temperature NCA polymerization at 0°C has the advantage that it is synthetically less demanding than other controlled NCA polymerization techniques, while offering very good control over the molecular weight and polydisper-sity. However, polymerization times are relatively long and the molecular weight is somewhat limited. 

Cheng and coworkers proposed hexamethyldisilazane as initiator for NCAs. The initial reaction results in a trimethylsilylcarbamate end group, which has a reduced reactivity compared to the amine (see Fig. lb). In the course of the polymerization, the trimethylsilyl group is transferred from the carbamate to the incoming monomer. In the work-up, the trimethylsilylcarbamate group is hydrolyzed and gives an amine group [15-17, 30]. 

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Methodologies for the de novo design and synthesis of polypeptides were recently developed. The preparation of periodic polypeptides, polypeptides containing artificial amino acids, polypeptides exhibiting rodlike structures, and hybrids of natural and artificial polypeptide segments was recently described [33],... 

A great deal of work has been done on the in situ activation of carboxylic acids toward nucleophilic substitution by amines. This type of reaction is fundamental for synthesis of polypeptides (see also Section 13.3.1). Dicyclohexylcarbodiimide... 

Over the past decade the techniques of combinatorial synthesis have received much attention. Solid phase synthesis of polypeptides and oligonucleotides are especially adaptable to combinatorial synthesis, but the method is not limited to these fields. The goal of combinatorial synthesis is to prepare a large number of related... 

In the synthesis of polypeptides with biological activity on a crosslinked polymer support as pioneered by Merrifield (1 2) a strict control of the amino acid sequence requires that each of the consecutive reactions should go virtually to completion. Thus, for the preparation of a polypeptide with 60 amino acid residues, even an average conversion of 99% would contaminate the product with an unacceptable amount of "defect chains". Yet, it has been observed (13) that with a large excess of an amino acid reagent —Tn the solution reacting with a polymer-bound polypeptide, the reaction kinetics deviate significantly from the expected exponential approach to quantitative conversion, indicating that the reactive sites on the polymer are not equally reactive. 

The insertion of unsaturated molecules into metal-carbon bonds is a critically important step in many transition-metal catalyzed organic transformations. The difference in insertion propensity of carbon-carbon and carbon-nitrogen multiple bonds can be attributed to the coordination characteristics of the respective molecules. The difficulty in achieving a to it isomerization may be the reason for the paucity of imine insertions. The synthesis of amides by the insertion of imines into palladium(II)-acyl bonds is the first direct observation of the insertion of imines into bonds between transition metals and carbon (see Scheme 7). The alternating copolymerization of imines with carbon monoxide (in which the insertion of the imine into palladium-acyl bonds would be the key step in the chain growth sequence), if successful, should constitute a new procedure for the synthesis of polypeptides (see Scheme 7).348... 

As early as five years after the Miller-Urey experiments, Schramm and Wissmann from the Max Planck Institute for Virus Research in Tubingen reported a successful synthesis of polypeptides using polyphosphate esters. Thus, they were able to... 

Prize in 1963 for inventing a new general method to synthesize important polymers, a method that uncovered much new basic science. A Nobel Prize in 1984 went to Robert Bruce Merrifield for his invention of a general approach to the synthesis of polypeptides and proteins, in a style directly reminiscent of the biological method used in such synthesis. 

The hydrophobic peptide segments of El and E2, which attach the spike protein to the lipid bilayer, can be localized on the polypeptide chains by a mapping procedure first used by Dintzis (1961) to show that the synthesis of polypeptide chains begins at the amino-terminal end. The hydrophobic stubs left in the viral membrane after protease treatment are found at the carboxyl-terminal ends of both the El and the E2 polypeptides (Garoff and Sdderlund, 1978). 

Vincent Du Vigneaud United States sulfur compounds of biological importance, synthesis of polypeptide hormone... 

Graft copolymers of nylon, protein, cellulose, starch, copolymers, or vinyl alcohol have been prepared by the reaction of ethylene oxide with these polymers. Graft copolymers are also produced when styrene is polymerized by Lewis acids in the presence of poly-p-methoxystyrene. The Merrifield synthesis of polypeptides is also based on graft copolymers formed from chloromethaylated PS. Thus, the variety of graft copolymers is great. 

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