Challenges in the design of insulin and relaxin/insulin-like peptide mimetics |
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Authors: | Mohammed Akhter Hossain Ross AD Bathgate |
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Institution: | 1. The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC 3010, Australia;2. School of Chemistry, University of Melbourne, Parkville, VIC 3010, Australia;3. Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, VIC 3010, Australia |
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Abstract: | Peptidomimetics are designed to overcome the poor pharmacokinetics and pharmacodynamics associated with the native peptide or protein on which they are based. The design of peptidomimetics starts from developing structure-activity relationships of the native ligand-target pair that identify the key residues that are responsible for the biological effect of the native peptide or protein. Then minimization of the structure and introduction of constraints are applied to create the core active site that can interact with the target with high affinity and selectivity. Developing peptidomimetics is not trivial and often challenging, particularly when peptides’ interaction mechanism with their target is complex. This review will discuss the challenges of developing peptidomimetics of therapeutically important insulin superfamily peptides, particularly those which have two chains (A and B) and three disulfide bonds and whose receptors are known, namely insulin, H2 relaxin, H3 relaxin, INSL3 and INSL5. |
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Keywords: | Peptides Insulin Insulin-like peptides Relaxin INSL5 |
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