In organic chemistry, peptide synthesis is the production of peptides, compounds where multiple amino acids are linked via amide bonds, also known as peptide bonds. Peptides are chemically synthesized by the condensation reaction of the carboxyl group of one amino acid to the amino group of another.

Racemization of amino acids is an inherent problem in liquid- and solid-phase peptide synthesis. Racemization can take place at several steps of the synthetic route: most important is the racemization of the amino acid during carboxy activation and coupling.

Peptide synthesis is the process of making short sequences of polypeptides by adding one amino acid at a time. This process is useful for creating specific sequences that represent epitopes of certain protein domains that may or may not be modified by moieties, such as phosphate groups.

The two major chemical techniques for peptide production are SPPS and solution phase synthesis (SPS). Classical SPS is based on the coupling of single amino acids in solution. The fragment condensation method has been used for the synthesis of long peptides.

Definition. Racemization is a process wherein optically active compounds (which consist of only one enantiomer) are converted into an equal mixture of enantiomers with zero optical activity (a racemic mixture). Racemization rates are dependent on the molecule and conditions such as pH and temperature.

Adding HOBt, 6-Cl-HOBt or HOAt suppresses the racemization. Protecting the pi imidazole nitrogen in the histidine side-chain with the methoxybenzyl group greatly reduces racemization.

An esterification is a condensation reaction in which an ester is formed from an alcohol and a carboxylic acid. Esterification is a subcategory of condensation reactions because a water molecule is produced in the reaction. The esterification reaction is reversible.

Peptide synthesis most often occurs by coupling the carboxyl group of the incoming amino acid to the N-terminus of the growing peptide chain. This C-to-N synthesis is opposite from protein biosynthesis, during which the N-terminus of the incoming amino acid is linked to the C-terminus of the protein chain (N-to-C).

The most commonly employed reagents, BOP, PyBOP, and HBTU generate OBt esters, and these have found wide application in routine SPPS and solution synthesis for difficult couplings. Coupling reagents are also available which generate esters that are more reactive than OBt.

The hydroxyl group could also induce a plethora of side reactions in peptide synthesis due to its evident nucleophilicity that mediates acyl migration, and consequent peptide fragmentation.

Amino group represents the most versatile nucleophile in peptide synthesis. Its acylation reaction is the underlying principle of the amino acid coupling and peptide chain elongation. Due to the high reactivity amino group could undertake a plethora of side reactions in the process of peptide synthesis.

Activation of the carboxyl group on either subjected amino acid building block or peptide segment that is supposed to be spliced to the reciprocal peptide fragment bearing to-be-acylated amino group or other relevant substituent constitutes one of the key steps in the peptide synthesis process.

Hydroxyl and carboxyl plays critical roles in peptide synthesis. The carboxyl group is the underlying basis for peptide bond construction.