Brain-enhanced delivery of neuroactive peptides by sequential metabolism

摘要: The invention provides novel peptide derivatives which are designed to deliver pharmacologically active peptides into the central nervous system by sequential metabolism. is placed in a molecular environment disguises its nature and biolabile, lipophilic functions penetrate blood-brain barrier passive transport. design incorporates dihydropyridine-type redox targetor moiety, an amino acid or di- tripeptide spacer inserted between N-terminal unit of bulky, substituent protecting C-terminal peptide. undergoes enzymatically mediated oxidation hydrophilic, membrane-impermeable pyridinium salt. That polar targetor-peptide conjugate trapped behind lipoidal barrier. Over time, cleavage ester from esterase and/or lipase enzymes enzymatic targetor-spacer results release desired brain.