Pharmaceuticals peptides

Fig. 6.4. Chemical, metabolic, and physical processes of instability in pharmaceutical peptides...

Apart from pharmaceuticals, peptides are also used for diagnostics and vaccines. More than 40 peptides are in commercial use today. A dozen of them is shown in Table 3.1. As shown in column 3 of the table, the number of amino acids that make up a specihc peptide varies widely. At the low end there are dipeptides, like the blockbuster antihypertensive drug enalapril and the artihcial sweetener Aspartame (not shown in the table). In terms of volumes produced, there are by far the most important product group. At the high end there is the anticoagulant Hirudin, which is composed of 65 amino acids. Sales of synthetic peptides are estimated at 4 billion as formulated drugs (resp. 300- 400 million as APIs). 

In terms of oral systems for peptide delivery, modern formulation technology ensures that the activity of pepsin can be avoided by using polymeric enteric coatings to protect the target pharmaceutical peptide. These coatings are resistant to the acid environment of the stomach but dissolve when the pH rises in the small intestine. It is absolutely essential that any formulation being considered for the oral delivery of therapeutic peptides be coated with such materials to ensure that the peptide is protected from the action of pepsin. 

TABLE 4 Analytical Methods for Characterization and Quality Control of Pharmaceutical Peptides and Proteins... 

Gilg, D., Riedl, B., Zier, A., and Zimmermann, M. F. (1996), Analytical methods for the characterization and quality control of pharmaceutical peptides and proteins, Pharm. Acta Helv., 71, 383-394. 

Costantino HR. Excipients for use in lyophilized pharmaceutical peptide, protein, and other bioproducts. In Pikal MJ, Costantino HR, eds. Lyophilization of Biomaterials. AAPS Press, 2004 139-228. 

Paratek Pharmaceuticals, Inc. PerSeptive Biosystems, Inc. Pharm-Eco Laboratories, Inc. Pharmaceutical Peptides, Inc. Phytera, Inc. polyORGANIX Inc. 

DNA may be the target of sequence changes (gene therapy), or interact witli small molecules (RNA, PNA, pharmaceuticals, peptides) or large proteins RNA may be target for small molecules, and proteins for small molecules or irrteracting large ones. 

Solution-phase synthesis, the synthesis of peptides in solution. Despite the dominance of solid-phase peptide synthesis (SPPS), solution-phase synthesis still is of importance for the synthesis of peptides on a larger scale, including the preparation of peptide pharmaceuticals. Peptide synthesis in solution may foUow either linear or convergent strategies. The linear synthesis is mostly employed for small peptides and peptide segments... 

See also. Nuclear Magnetic Resonance Spectroscopy Principles. Nuclear Magnetic Resonance Spectroscopy-Applicable Elements Carbon-13 Nitrogen-15. Nuclear Magnetic Resonance Spectroscopy Applications Pharmaceutical. Peptides. Structural Elucidation. 

The Rollgen s group [9] reports the thermal desorption of [M + Alkah]" quasi-molecular ions from a electrically heated metal smface (wires or ribbons) for so-dimn alkah salts of carboxylic acids and mixtures of alkali halides with a crown ether, glucose and adenosine. With benzo-15-crown-5 the desorption of [M + Na]" ions takes place even below the threshold temperature for thermionic emission of alkah ions. Alkali ion attachment has also been performed by thermal desorption of thermally labile analytes such as saccharides, pharmaceuticals, peptides, steroids and their mixtirres. Bombick and Alhson [8] describe a desorption/ioniza-tion method where samples are deposited directly on thermionic emission materials (lK20 lAl203 2Si02) and heated within the mass spectrometer s source. Ions representative of the sample are formed. The proposed mechanism involves the gas-phase addition of emitted potassium ions to neutrals desorbed from the surface. 

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