title: Structure of synthetic peptide analogues of an eggshell protein of Schistosoma mansoni.
abstract: The peptide (Gly-L-Tyr-L-Asp-L-Lys-L-Tyr)6, referred to as F4-6, was synthesized as a model for a schistosome eggshell protein in which the Gly-Tyr-Asp-Lys-Tyr consensus sequence is repeated over 40 times. Analysis by CD, Fourier transform infrared spectroscopy, potentiometric and spectrophotomertric titrations, NMR, and molecular modeling suggests that F4-6 forms some type of left-handed structure. A likely possibility appears to be a left-handed alpha-helix stabilized by Lysi-Aspi +4 salt bridges and possibly Aspi-Tyri +4 hydrogen bonding and Tyr-Tyr interactions. Spectroscopic studies of a number of F4-6 analogues support this conclusion. For example, substitution of D-Ala for Gly produces a peptide with enhanced left-handed helical spectral characteristics, whereas an L-Ala substitution results in a peptide with minimal structure. These studies suggest that the F4 protein from Schistosoma mansoni may be the first example of a naturally occurring protein devoid of proline and carbohydrate that forms a left-handed helix composed of L-amino acids, although alternative forms of other left-handed structures have yet to be rigorously excluded.
authors.affiliation: Department of Pharmaceutical Research, Merck Research Laboratories, West Point, Pennsylvania 19486.
authors.forename: C R
authors.initials: CR
authors.lastname: Middaugh
authors.forename: J A
authors.initials: JA
authors.lastname: Thomson
authors.forename: C J
authors.initials: CJ
authors.lastname: Burke
authors.forename: H
authors.initials: H
authors.lastname: Mach
authors.forename: A M
authors.initials: AM
authors.lastname: Naylor
authors.forename: M J
authors.initials: MJ
authors.lastname: Bogusky
authors.forename: J A
authors.initials: JA
authors.lastname: Ryan
authors.forename: S M
authors.initials: SM
authors.lastname: Pitzenberger
authors.forename: H
authors.initials: H
authors.lastname: Ji
authors.forename: J S
authors.initials: JS
authors.lastname: Cordingley
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002942:Circular Dichroism; D016384:Consensus Sequence; D004527:Egg Proteins / Q000737:chemistry* / Q000235:genetics; D005260:Female; D015801:Helminth Proteins / Q000737:chemistry* / Q000235:genetics; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D011487:Protein Conformation; D012550:Schistosoma mansoni / Q000737:chemistry* / Q000235:genetics; D013055:Spectrophotometry, Infrared; D013816:Thermodynamics
chemical_list: D004527:Egg Proteins; D015801:Helminth Proteins; D010455:Peptides