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- W96850176 endingPage "601" @default.
- W96850176 startingPage "573" @default.
- W96850176 abstract "Polypeptides and proteins perform critical control and signaling functions in all tissues in the body and typically display high potency with low toxicity. However as candidate pharmaceuticals they have suffered from several limitations: short duration of action, limited receptor subtype selectivity, and low oral bioavailability. There are now general medicinal chemical and drug delivery approaches to answer each of these challenges. Truncation and modification lead to smaller agonists or antagonists. Duration of peptide action has been addressed with unnatural amino acid substitutions that alter physical properties to cause in vivo depoting effects, that block proteolysis or that rigidify the structure to address specificity issues. Modification by acylation, PEGylation, and protein conjugation prevent rapid clearance by glomerular filtration in the kidney. Modification of peptide/protein structural motifs brings these medicinal chemistry approaches into the protein realm. Drug delivery approaches have tremendous potential to add value, primarily through controlled-release injectable (to once yearly), intranasal, and inhalation routes of administration. Advances in protein and peptide manufacture, coupled with the completion of the Human Genome Project, mean that there is an abundance of feasible new targets. While peptidomimetic approaches are making tremendous strides, there remains a large and valuable role for modified peptide and protein pharmaceuticals in medicine. This chapter provides an overview of current, practical approaches to successful peptide pharmaceuticals." @default.
- W96850176 created "2016-06-24" @default.
- W96850176 creator A5049562432 @default.
- W96850176 date "2007-01-01" @default.
- W96850176 modified "2023-09-25" @default.
- W96850176 title "Peptide and Protein Drugs: Issues and Solutions" @default.
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