Structure-activity study of a laminin alpha 1 chain active peptide segment Ile-Lys-Val-Ala-Val (IKVAV).
The IKVAV sequence, one of the most potent active sites of laminin-1, has been shown to promote cell adhesion, neurite outgrowth, and tumor growth. Here we have determined the structural requirements of the IKVAV sequence for cell attachment and neurite outgrowth using various 12-mer synthetic peptide analogs. All-L- and all-D-IKVAV peptides showed cell attachment and neurite outgrowth activities. In contrast, all-L- and all-D-reverse-sequence peptides were not active. Some of the analogs, in which the lysine and isoleucine residues of the IKVAV peptide were substituted with different amino acids, promoted cell attachment, but none of the analog peptides showed neurite outgrowth activity comparable to that of the IKVAV peptide. These results suggest that the lysine and isoleucine residues are critical for the biological functions of the IKVAV peptide.
Nomizu
M
M
Laboratory of Developmental Biology, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892, USA.
Weeks
B S
BS
Weston
C A
CA
Kim
W H
WH
Kleinman
H K
HK
Yamada
Y
Y
D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007700:Kinetics; D007797:Laminin / Q000737:chemistry* / Q000494:pharmacology*; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D016501:Neurites / Q000187:drug effects* / Q000502:physiology; D016716:PC12 Cells; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D007797:Laminin; D046911:Macromolecular Substances; D010446:Peptide Fragments; C083321:isoleucyl-lysyl-valyl-alanyl-valine