Current Pharmaceutical Biotechnology - Volume 3, Issue 4, 2002

Therapeutic proteins have been engineered for a variety of purposes including reduced antigenicity, longer halflife, simplified process development, and increased affinity. Fusion proteins bring together functions from two different molecules creating therapeutics with completely novel activities. Protein engineering technologies have relied on rational design, directed evolution, DNA shuffling, RNA-peptide fusion, p Read More

This review considers chemical and genetic approaches to the modification of protein structure. The historical interest in chemical and site-directed modifications will be briefly covered. Current chemical modification strategies will be presented. Biosynthetic mutagenesis with unnatural aminoacyl-tRNAs and current synthetic peptide ligation technologies will be covered in greater detail. The application of combinatorial g Read More

Traditionally, the development of drugs has focused on small molecule therapeutics. However, with recent advances in recombinant protein technology the potential of proteins as therapeutics is starting to be realized. Already there are protein drugs on the market, including naturally occurring proteins, engineered proteins and proteins introduced into the patient by way of gene therapy. The next generation of such dr Read More

Protein folding, the problem of how an amino acid sequence folds into a unique three-dimensional shape, has been a long-standing problem in biology. The success of genome-wide sequencing efforts has increased the interest in understanding the protein folding enigma, because realizing the value of the genomic sequences rests on the accuracy with which the encoded gene products are understood. Although a complete Read More

There is a large and increasing number of therapeutic proteins approved for clinical use and many more undergoing preclinical studies and clinical trials in humans. Most of them are human or “humanized” recombinant molecules. Virtually all therapeutic proteins elicit some level of antibody response, which in some cases, can lead to potentially serious side effects. Therefore, immunogenicity of therapeutic proteins is a conce Read More

Efficient development of stable formulations of protein pharmaceuticals requires an intimate knowledge of the protein and its chemical and physical properties. In particular, understanding the mechanisms by which a protein could degrade is critical for designing and testing formulations. This review describes the major pathways by which proteins can degrade, including denaturation, aggregation, oxidation, and interfacial Read More