Engineering of a Novel Simplified Human Insulin-Like Peptide 5 Agonist
作者： Nitin A. Patil , Richard A. Hughes , K. Johan Rosengren , Martina Kocan , Sheng Yu Ang
DOI: 10.1021/ACS.JMEDCHEM.5B01786
关键词:
摘要: Insulin-like peptide 5 (INSL5) has recently been discovered as only the second orexigenic gut hormone after ghrelin. As we have previously reported, INSL5 is extremely difficult to assemble and oxidize into its two-chain three-disulfide structure. The focus of this study was generate structure–activity relationships (SARs) use it develop a potent simpler mimetic with RXFP4 agonist activity. A series human mouse (hINSL5/mINSL5) analogues were designed chemically synthesized, resulting in chimeric analogue exhibiting more than 10-fold higher potency (0.35 nM) at compared native hINSL5 (4.57 nM). SAR also identified key residue (KA15) A-chain mINSL5 that contributes improved affinity hINSL5. This knowledge ultimately led us engineer minimized retains hINSL5-like RXFP4. s...
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