Abstract
Peptides are considered to be excellent candidates for therapeutics, mainly due to their specificity, safety, tolerability, and efficacy profiles in humans. Although many therapeutics are inspired from nature, naturally occurring peptides are often unsuitable for use as convenient therapeutics, because of limitations such as poor chemical and physical stability, and a short circulating plasma half-life. Structural design of peptides is of utmost importance to overcome these shortcomings, and this strategy may lead to the design of high-quality bioactive peptides. In principle, peptides and proteins could have several valuable applications in medicine, but so far, applications of synthetic peptides have been severely limited by poor membrane permeability, high clearance, low systemic stability, and negligible activity when administered orally. The focus of chapter 6 is the structural design of bioactive peptide-based drugs. The structural design of bioactive peptides is subdivided into different strategies such as metal complexation, terminus and side-chain modifications and cyclizations. It is highly likely that the future of structural design and development of therapeutic peptides depends on the judicious use of diverse classes of unnatural amino acids.
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