Molecule

Industrial peptide synthesis

Even though the structure of peptides was discovered a century ago, it wasn’t until Du Vigneaud’s synthesis of oxytocin some 50 years later that the peptide field was truly propelled and pharmaceutical usage of peptides began

Since then, this field has taken some giant leaps, and production of peptides of any size and complexity is now possible. Perhaps the most significant of all techniques was Merrifield’s publication of the solid-phase peptide synthesis (SPPS) method, which entirely revolutionized the peptide production, not only from the viewpoint of research but also because of its present widespread use for the manufacture of peptides which are used as active pharmaceutical ingredients (APIs).

Three basic strategies adopted in preparation of peptides are:-

 

  • Solution-Phase Methods
  • Solid-Phase Methods
  • Hybrid Approaches

Solution-Phase Methods

Most of the peptide pharmaceuticals presently are manufactured using solution-phase methodology. While the method can be useful for the production of longer peptides and even some small proteins, but the technique is mostly used to produce small or medium-length peptides. Products include angiotensin converting enzyme (ACE) inhibitors, Aspartame, the dipeptides sweetener, oxytocin, HIV protease inhibitors and LH-RH analogues.

 

Solid-Phase Methods

This technique is highly useful because it could be automated, leading to rapid production of quite complex sequences. Initially as the technique was proposed there were some doubts regarding to purification methods however, since increasingly powerful analytical methods and purification techniques have become available, the technique has been increasingly used for manufacturing a number of commercial products, such as LH-RH and, Somatostatin and salmon calcitonin

Hybrid Approaches

While both the solution-phase and solid-phase approaches have proven to be effective for the production of a relatively extensive variety of products, both strategies have their own limitations. With the introduction of newer resins. This has unlocked the possibility of a “hybrid” approach, in which the manufacture of complex sequences is approached through the solid-phase synthesis of large fragments, that are then assembled.