Total Solid-Phase Synthesis of Biologically Active Drosophila Insulin-Like Peptide 2 (DILP2)

Australian Journal of Chemistry
Feng LinJohn D Wade

Abstract

In the fruit fly Drosophila melanogaster, there are eight insulin-like peptides (DILPs) with DILPs 1-7 interacting with a sole insulin-like receptor tyrosine kinase (DInR) while DILP8 interacts with a single G protein-coupled receptor (GPCR), Lgr3. Loss-of-function dilp mutation studies show that the neuropeptide DILP2 has a key role in carbohydrate and lipid metabolism as well as longevity and reproduction. A better understanding of the processes whereby DILP2 mediates its specific actions is required. Consequently we undertook to prepare DILP2 as part of a larger, detailed structure-function relationship study. Use of our well-established insulin-like peptide synthesis protocol that entails separate solid phase assembly of each of the A- and B-chains with selective cysteine S-protection followed by sequential S-deprotection and simultaneous disulfide bond formation produced DILP2 in good overall yield and high purity. The synthetic DILP2 was shown to induce significant DInR phosphorylation and downstream signalling, with it being more potent than human insulin. This peptide will be a valuable tool to provide further insights into its binding to the insulin receptor, the subsequent cell signalling and role in insect metabolism.

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Citations

Mar 30, 2019·Chemistry : a European Journal·Nitin A PatilJulien Tailhades
Oct 8, 2020·Genetics·Michael J TexadaKim Rewitz
Jan 24, 2021·The Journal of Biological Chemistry·Yan-Li LiXiao-Fan Zhao
May 7, 2021·Genetics·Michael J TexadaKim Rewitz
Jun 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Nannan LiuShikai Liu
Nov 28, 2017·Journal of Medicinal Chemistry·Kateřina MacháčkováJiří Jiráček
Aug 23, 2017·Accounts of Chemical Research·Mohammed Akhter Hossain, John D Wade

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Methods Mentioned

BETA
electrophoresis
Reverse Transcription Polymerase Chain Reaction

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