Identification of neurite extension inducing peptides by means of soluble combinatorial peptide libraries.
To identify hexapeptides capable of inducing neurite outgrowth, we used three groups of soluble combinatorial peptide libraries each consisting of 100 mixtures of hexapeptides (each mixture consisting of 10,000 individual peptides) with partially predetermined sequences (in two out of six amino acid positions). Using this approach a number of neuritogenic peptides were identified. Three selected peptides, QSGKKF, QSGPLA and QSGKQG, were found to induce neurite outgrowth from primary hippocampal neurons with potency comparable to that of growth factors. None of the peptides protected cerebellar granule neurons from cell death induced by withdrawal of potassium chloride. The approach described here suggests the feasibility to use combinatorial peptide libraries in order to identify compounds capable of modulating a specific functional response in the nervous system, without prior knowledge of a molecular target.
Ralets
Igor
I
Protein Laboratory, Institute of Molecular Pathology, Panum Institute Bld.6.2., Blegdamsvej 3c, DK-2200 Copenhagen N, Denmark.
Østergaard
Søren
S
Holm
Arne
A
Køhler
Lene
L
Bock
Elisabeth
E
Berezin
Vladimir
V
D000595:Amino Acid Sequence / Q000502:physiology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002525:Cerebellar Cortex / Q000166:cytology / Q000187:drug effects / Q000254:growth & development; D020650:Combinatorial Chemistry Techniques; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D005333:Fetus; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000254:growth & development; D008024:Ligands; D009414:Nerve Growth Factors / Q000138:chemical synthesis / Q000302:isolation & purification* / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D009448:Neurochemistry / Q000379:methods*; D018696:Neuroprotective Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D019151:Peptide Library; D010455:Peptides / Q000138:chemical synthesis / Q000302:isolation & purification* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D008024:Ligands; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D019151:Peptide Library; D010455:Peptides