Then, the enzymatic synthesis of peptides

The feasibility of scale-up for applications of enzymatic solid-to-solid synthesis of dipeptides was investigated by using Thermoase catalyzed synthesis of Z-Asp-Phe-OMe as a model reaction. The reaction system involves typically only 10% (w/w) enzyme suspension added to dry solid substrates. Enzymatic solid-to-solid biocatalysis combines the main advantages of aqueous media, high catalytic activity, low water media, and high yields. A flow sheet for the whole process is described, as well as the use of a jacketed reactor with an anchor stirrer for various steps of the process, including the neutralization reaction to adjust the acid-base condition of the reaction mixture. A solution for enzyme recycling, an important issue for scale-up applications, is also suggested.

An example of orthogonality in convergent synthesis

project on enzymatic peptide synthesis within DSM Innovative Synthesis B.V.

Some relevant examples are the synthesis of

An example of orthogonality in convergent synthesis is the combination of t-Boc/Bzl and Fmoc/tBu using supports whose linkage to the peptide can be either labile to acid, base, palladium or photolabile.

Useful methods in enzymatic synthesis of peptides: a

Some typical examples of this methodology are the synthesis of phospholipase A (124 residues with 14 cysteine residues and 7 disulfide bridges), the synthesis of the microprotein S (


Enzymatic Peptide Synthesis: from the Substrate Point …

Despite these drawbacks, solid-phase synthesis has many advantages over the classical system in solution: the reaction can be automated and the problem of solubilization of the peptide no longer exists since it remains attached to the solid matrix.

New developments in enzymatic peptide synthesis - …

Some relevant examples are the synthesis of the leading non-caloric sweetener aspartame, the lysine sweet peptide, kyotorphin, angiotensin, enkephalin and dynorphin (;

Enzymatic peptide synthesis in low water content …

When Merrifield introduced the method of solid-phase synthesis in 1963, the scientific community reacted with skepticism: the synthesis in solution was at that time well established and in the new proposed system the purification of the peptide could only be done after cleavage, with the concomitant cleavage of most of the byproducts accumulated during the synthesis (

protecting group in chemical and enzymatic peptide synthesis; ..

In biphasic systems, the partition of the peptide products from the aqueous phase that contains the enzyme to the organic phase drives the equilibrium towards synthesis, with the additional benefit that the product is no longer subjected to hydrolysis.

Enzymatic synthesis of a CCK-8 tripeptide fragment in organic media.

However, the replacement of piperidine by stronger bases has circumvented the problem of incomplete deprotection in Fmoc/tBu solid phase synthesis of β-peptides () and longer β-peptides and mixed type α-β-peptides have been successfully synthesized by chemical ligation (

Solid-phase synthesis of b-oligopeptides.

Solid supports should meet several requirements: particles should be of conventional and uniform size, mechanically robust, easily filterable, chemically inert and chemically stable under the conditions of synthesis and highly accessible to the solvents allowing the penetration of the reagents and the enlargement of the peptide chain within its microstructure.

Enzymatic synthesis of cholecystokinin-octapeptide.

Commonly, peptides of less than 30 residues are produced entirely by solid phase sequential synthesis (), while larger peptides (up to 60 residues) must be produced by convergent synthesis in which protected peptide fragments are synthesized by SPPS and then combined by liquid phase synthesis (