Discovery, synthesis, and biological evaluation of apratyramide, a marine-derived transcriptional stimulator of VEGF-A

Abstract

A collection of the marine cyanobacterium Moorea bouillonii from Apra Harbor in Guam afforded apratyramide, a linear depsipeptide consisting of four amino acid residues and one hydroxy acid moiety. The structure was elucidated by a combination 1D/2D NMR spectroscopic and mass spectrometric analysis. The absolute configuration of the stereocenters was determined by LC-MS analysis of the acid hydrolyzate. Apratyramide was then synthesized and tested for bioactivity. Apratyramide induced the transcription and secretion of vascular endothelial growth factor A (VEGF-A) in multiple cell types. This activity is being explored for various applications where VEGF-A upregulation would be beneficial.