Peptides physical instability

Reubsaet JL, Beijnen JH, Bult A, et al. Analytical techniques used to study the degradation of proteins and peptides physical instability. J Pharm Biomed Anal 1998 17(6-7) 979-984. 

All proteins and peptides display chemical and physical instability that affects the way they are distributed and cleared in the body and their delivery to the site of action. Physical and chemical instability is affected by primary sequences and secondary and tertiary structures and the degree of glyco-sylation of protein. Chemical degradation of proteins and peptides involves deamidation, racemization, hydrolysis, oxidation, beta elimination, and disulfide exchange. Physical degradation of proteins involves denaturation and aggregation. 

Proteins, peptides, and other polymeric macromolecules display varying degrees of chemical and physical stability. The degree of stability of these macromolecules influence the way they are manufactured, distributed, and administered. Chemical stability refers to how readily the molecule can undergo chemical reactions that modify specific amino-acid residues, the building blocks of the proteins and peptides. Chemical instability mechanisms of proteins and peptides include hydrolysis, deamidation, racemization, beta-elimination, disulfide exchange, and oxidation. Physical stability refers to how readily the molecule loses its tertiary and/or sec-... 

Physical instability is a phenomenon which is rarely encountered with small organic molecules but arises in peptides and proteins because of the many conditions under which... 

Delivery of large-molecular-weight, biotechnology-produced drugs info the body is difficult because of the poor absorption of these compounds, the acid lability of peptide bonds, and the rapid enzymatic degradation of these drugs in the body. In addition, protein pharmaceuticals are susceptible to physical instability, complex feedback control mechanisms, and peculiar dose-response relationships. 

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

The stability of biotechnology-produced products, proteins (macromolecules), and peptides is unique when compared with conventional pharmaceuticals (small molecules). Protein degradation by both chemical and physical processes leads to the loss of biological activity, whereas peptides decompose only through chemical instability with loss of efficacy and produce undesirable biological effects. 

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