The peptide ghrelin is the endogenous ligand for the growth-hormone secretagogue receptor (GHSR-1a), also referred to as the ghrelin receptor. While the primary role of ghrelin relates to appetite regulation, there is increasing evidence for the cancer associated implications of the presence of the GHSR. We are developing a variety of fluorine-containing ghrelin analogues for the purpose of molecular imaging of the GHSR-1a and as potential diagnostic-therapeutic pairs. While natural 28-mer ghrelin (IC50 = 3.1 nM) has poor in vivo stability, we have developed ghrelin(1-8) analogues with fluorine-containing side-chains that have improved receptor affinity and serum stability. Modifications at positions 1, 3, 4, and 8 resulted in low MW octapeptides with receptor affinity superior to that of full length ghrelin (IC50 = 0.1 nM). Peptidomimetics containing fluorine, based upon the growth hormone secretagogue G-7039, have also been developed with sub-nanomolar GHSR-1a affinity. These ghrelin receptor targeting peptides and peptidomimetics have been successfully radiolabelled with 18F for PET imaging, while also having the potential to be used as peptide therapeutics with natural 19F.

Fluorinated peptides and peptidomimetics targeting the ghrelin receptor (GHSR-1a)

255th National Meeting (2018)

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