Amphiphilic helix is essential for the activity of brain injury‐derived neurotrophic peptide (BINP)

[摘要]

To study the structure-activity relationships of brain injury-derived neurotrophic peptide (BINP), 12 analogs were synthesized by replacing each amino acid residue with Gly. BINP showed CD spectra typical of an α-helical conformation in TFE solution which mimics the membrane environment. In the α-helical conformation, BINP showed an amphiphilic profile. Neurotrophic activities of BINP and its analogs were estimated from the effects on supporting septal cholinergic neurons and on rescuing hippocampal neurons from injury caused by glutamate. Both assays showed that the residues on the hydrophobic side of the amphiphilic helix were essential for the neurotrophic activity.

[学科分类] 生物化学/生物物理

[关键词] Neurotrophic peptide;Amphiphilic helix;Cholinergic neuron;Hippocampal neuron;BINP;brain injury-derived neurotrophic peptide;Boc;t-butoxycarbonyl;ChAT;choline acetyltransferase;DMEM;Dulbecco's modified Eagle's medium;FAB-MS;fast atom bombardment mass spectrometry;HPLC;high performance liquid chromatography;Fmoc;9-fluorenylmethoxycarbonyl;NGF;nerve growth factor;ODS;octadecylsilane;TFA;trifluoroacetic acid;TFE;trifluoroethanol;Analogs are designated by a letter and number indicating the identity and position of the replaced amino acid;followed by a letter indicating the identity of the replacement;for example;E1G indicates an analog in which Glu1 is replaced with Gly