Activity-dependent neurotrophic factor, ADNF, determines the structure characteristics of Colivelin, a fusion protein of ADNF9 and Humanin analog.
A 24-amino acid long peptide, Humanin, protects neurons from Alzheimer's disease (AD)-related cell toxicities at sub-nM-uM concentrations. Activity-dependent neurotrophic factor (ADNF) is a glia-derived neurotrophic peptide, which protects neurons from tetrodoxin treatment and AD-related and amyotrophic lateral sclerosis-related insults at fM concentrations. An attempt was made to further improve the activity of Humanin by fusing this peptide to ADNF9, a 9-amino acid long core peptide of the ADNF. This fusion resulted in a novel molecule, termed Colivelin, with the neuroprotective activity at fM range, which is approximately 10(3)-10(7) fold higher than the activity of Humanin and Humanin analogs and follows the activity profile of fM-active ADNF9. We have characterized the structural properties of Colivelin and compared with those of ADNF9 and Humanin in water and phosphate-buffered saline (PBS). The secondary structure of Colivelin was similar to that of ADNF9, but not that of Humanin, and hence was not the average of the contributions of the two peptides fused. Colivelin was stable and monomeric in PBS, consistent with the monomeric property of ADNF9, while Humanin showed strong tendency to self-associate. Thus, it is evident that the structural properties of Colivelin resemble those of ADNF9, rather than those of Humanin.
Arakawa
Tsutomu
T
Alliance Protein Laboratories, Thousand Oaks, CA 91360, USA. tarakawa2@aol.com
Niikura
Takako
T
Arisaka
Fumio
F
Kita
Yoshiko
Y
D000595:Amino Acid Sequence; D002942:Circular Dichroism; D004355:Drug Stability; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry* / Q000235:genetics; D008969:Molecular Sequence Data; D015394:Molecular Structure; D046912:Multiprotein Complexes / Q000737:chemistry; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics; D009842:Oligopeptides / Q000737:chemistry* / Q000235:genetics; D017433:Protein Structure, Secondary; D012996:Solutions; D014461:Ultracentrifugation
C508523:Colivelin; D047908:Intracellular Signaling Peptides and Proteins; D046912:Multiprotein Complexes; D009419:Nerve Tissue Proteins; D009842:Oligopeptides; D012996:Solutions; C410622:activity-dependent neurotrophic factor; C427211:humanin