Insulin and insulin-like peptide hormones have a diverse range of physiological functions.1 Their clinical importance is highlighted by the fact that insulin, until today, remains the primary treatment for diabetes (particularly of type 1), and human relaxin-2 is in the clinic for the treatment of acute heart failure. Insulin-like peptides possess a very complex structure with 2 chains and 3 disulphide bridges. Currently, these peptides are produced by recombinant gene expression technology which has known problems and limitations, particularly in the folding of non-native peptide analogs. My team has developed novel chemical methods2-4 that enabled us to carry out details SAR studies of these peptides leading to the generation of simplified peptidomimetics that target the G protein coupled receptors, RXFP1, 3 and 4.5-8 These novel compounds offer safer and cheaper treatment options as they are target-specific and easier to prepare compared with native molecules.
References
1 N. Patil… & M. A. Hossain, British Journal of Pharmacology, 2016, doi: 10.1111/bph.13684.
2 J. Karas, M. A. Hossain, Chemistry: A European Journal, 2014, 20, 9549-9552.
3 J. Karas…& M. A. Hossain, Angewandte Chemie International Edition, 2016, 55, 14743-14747.
4 N. Patil… & M. A. Hossain, Angewandte Chemie International Edition, 2016, 55, 14552-14556.
5 A. Sethi…& M. A. Hossain…. & P. Gooley, Nature Communications, 2016, 7, 11344.
6 M. A. Hossain, M. A….& C. S. Samuel, Chemical Science, 2016, 7, 3805-3819.
7 N. Patil…& M. A. Hossain, Journal of Medicinal Chemistry, 2016, 59, 2118-2125.
8 K. Hojo, M. A. Hossain…. & R. A. Bathgate, Journal of Medicinal Chemistry, 2016, 59, 7445-7456.