Folding and activity of hybrid sequence, disulfide-stabilized peptides.
Peptides have been synthesized that have hybrid sequences, partially derived from the bee venom peptide apamin and partially from the S peptide of ribonuclease A. The hybrid peptides were demonstrated by NMR spectroscopy to fold, forming the same disulfides and basic three-dimensional structure as native apamin, containing a beta-turn and an alpha-helix. These hybrids were active in complementing S protein, reactivating nuclease activity. In addition, the hybrid peptide was effective in inducing antibodies that cross-react with the RNase, without conjugation to a carrier protein. The stability of the folded structure of this peptide suggests that it should be possible to elicit antibodies that will react not only with a specific sequence, but also with a specific secondary structure. Hybrid sequence peptides also provide opportunities to study separately nucleation and propagation steps in formation of secondary structure. We show that in S peptide the alpha-helix does not end abruptly but rather terminates gradually over four or five residues. In general, these hybrid sequence peptides, which fold predictably because of disulfide bond formation, can provide opportunities for examining structure-function relationships for many biologically active sequences.
Pease
J H
JH
Department of Chemistry, University of California, Berkeley 94720.
Storrs
R W
RW
Wemmer
D E
DE
D000595:Amino Acid Sequence; D000818:Animals; D001030:Apamin; D001514:Bee Venoms; D004220:Disulfides; D004797:Enzyme-Linked Immunosorbent Assay; D007106:Immune Sera; D046911:Macromolecular Substances; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis; D011487:Protein Conformation; D012335:RNA, Ribosomal / Q000378:metabolism; D011817:Rabbits; D012259:Ribonuclease, Pancreatic / Q000378:metabolism
D001514:Bee Venoms; D004220:Disulfides; D007106:Immune Sera; D046911:Macromolecular Substances; D010455:Peptides; D012335:RNA, Ribosomal; D001030:Apamin; D012259:Ribonuclease, Pancreatic