The Basic Principle Of Peptide Bond Formation In Peptide Synthesis

November 13, 2019

The formation of a peptide bond, on the surface, is a brief chemical process. It refers to the dehydration of two amino acid components through a peptide bond.

Peptide bonds are formed by activating some carboxyl groups of an amino acid (A) and some carboxyl groups of the second amino acid (B), which are nucleophilic and invade some of the activated carboxyl groups, to form dipeptides (A-B). Assuming that the amino group of the carboxyl component (A) is unprotected, the composition of the peptide bond can not be manipulated. Perhaps there are by-products such as linear and cyclic peptides, which are mixed with the policy compound A-B. Therefore, in the process of polypeptide formation, it is necessary to protect all functional groups that do not participate in the formation of peptide bonds in a temporary reversible way.

Peptide Composition - The composition of each peptide bond, which consists of three steps:

1. Some protected amino acids need to be prepared, and the amphoteric structure of amino acids no longer exists.

2. In order to form a two-step reaction of peptide bond, it is necessary for the carboxyl group of N-protected amino acid to be activated as an active intermediate first, and then to form a peptide bond. This coupling reaction can be carried out either as a one-step reaction or as two consecutive reactions.

3. Selective removal or total removal of the protective base. Although all removal takes place after the complete assembly of the peptide chain, selective removal of the protective group is also necessary in order to continue the composition of the peptide.

Because 10 amino acids (Ser, Thr, Tyr, Asp, Glu, Lys, Arg, His, Sec and Cys) are rich in side chain functional groups that need selective protection, the composition of the peptide becomes more disordered. Because there are different appeals for selectivity, it is necessary to distinguish between temporary and semi-permanent protection bases. Temporary protectors are used for the temporary protection of amino or carboxyl functional groups of amino acids to be reacted next. They are removed without disturbing the semi-permanent protectors of peptide bonds or side chains of amino acids, sometimes in the process of formation.

In an ambitious state, the activation of carboxyl components and subsequent peptide bond formation (coupling reaction) should be a rapid reaction, without racemization or by-product composition, and the use of equimolar reactants to achieve high yields. However, it is disappointing that there is no chemical coupling method to satisfy these requests, and few methods are suitable for the composition of practice.

In the process of peptide formation, functional groups involved in multiple reactions are often linked to a chiral base (glycine is the only exception), and there is a potential risk of episodic racemization.

Peptides constitute the ultimate step in the cycle, and the protective base is removed completely. In addition to the need for complete deprotection in the composition of dipeptides, selective deprotector removal is very important for the extension of the peptide chain. Strategies should be carefully considered and selected according to the strategy to selectively remove Nalpha-amino or carboxyl protectors. The term "strategy" here refers to the sequence of condensation reactions of individual amino acids. Generally speaking, there is a difference between gradual composition and fragment condensation. In most cases, the method of gradual extension of peptide chains can only form short fragments for difficult sequences. To construct longer peptides, it is necessary for policy makers to segment into appropriate fragments and determine that they can minimize the degree of differential isomerization of the C-terminal during fragment condensation. After the individual fragments are assembled step by step, the policy compounds are linked. Peptide composition tactics include selecting the most appropriate combination of protective bases and the best method of fragment coupling.