High-yield, solid-phase synthesis of humanin, an Alzheimer's disease associated, novel 24-mer peptide which contains a difficult sequence.
Humanin is a novel, 24-mer residue bioactive peptide, which antagonizes Alzheimer's disease (AD) related neurotoxicity and offers a hope for developing new therapeutics against AD. Access to adequate amounts of pure humanin is a prerequisite for further, thorough, investigation of the pharmacological properties and therapeutic potency of the peptide. Until now, humanin has been obtained mainly by molecular biology techniques. In this work the Fmoc solid-phase synthesis of humanin on an in-house prepared 2-Cl-tritylamidomethyl polystyrene resin is described fully. Special precautions, i.e. prolonged deprotection steps, should be taken to achieve a high overall yield, since humanin seems to contain a 'difficult sequence' (R4G5F6S7C8L9) near its highly lipophilic, biologically important region L9L10L11L12.
Evangelou
Alexandra
A
Immunopeptide Chemistry Laboratory, Institute of Radioisotopes-Radiodiagnostic Products, NCSR 'Demokritos', Athens 153 10, Greece.
Zikos
Christos
C
Livaniou
Evangelia
E
Evangelatos
Gregory P
GP
D000544:Alzheimer Disease / Q000188:drug therapy; D020650:Combinatorial Chemistry Techniques; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D018696:Neuroprotective Agents / Q000138:chemical synthesis*; D010455:Peptides / Q000138:chemical synthesis*; D011506:Proteins / Q000138:chemical synthesis
D047908:Intracellular Signaling Peptides and Proteins; D018696:Neuroprotective Agents; D010455:Peptides; D011506:Proteins; C427211:humanin