Linear Peptides Containing d‑Leucine with Neuroprotective Activities from the Leech Whitmania pigra Whitman

Three new linear peptides containing d-leucine, named whitmantides A–C (13), were isolated from the dried whole bodies of Whitmania pigra Whitman. Their structures with absolute configurations were elucidated by Edman degradation, mass spectrometry, Marfey’s analysis, and solid-phase synthesis. It is the first time that peptides containing d-amino acid in leeches were discovered. Compounds 13 displayed neuroprotective activities against oxygen–glucose deprivation/reperfusion injury on Neuro-2a cells. In addition, ex vivo serum stability tests showed that 13 were resistant to protease degradation.