TY - JOUR
T1 - A recipe for designing water-soluble, β-sheet-forming peptides
AU - Mayo, Kevin H.
AU - Ilyina, Elena
AU - Park, Henry
PY - 1996/7
Y1 - 1996/7
N2 - Based on observations of solubility and lording properties of peptide 33-mers derived from the β-sheet domains of platelet factor-4 (PF4), interleukin-8 (IL-8), and growth related protein (Gro-α), as well as other β-sheet-forming peptides, general guidelines have been developed to aid in the design of water soluble, self association-induced β-sheet-forming peptides. CD, 1H-NMR, and pulsed field gradient NMR self-diffusion measurements have been used to assess the degree of folding and state of aggregation. PF4 peptide forms native-like β-sheet tetramers and is sparingly soluble above pH 6. IL-8 peptide is insoluble between pH 4.5 and pH 7.5, yet forms stable, native-like β-sheet dimers at higher pH. Gro-α peptide is soluble at all pH values, yet displays no discernable β-sheet structure even when diffusion data indicate dimer tetramer aggregation. A recipe used in the de novo design of water-soluble β-sheet-forming peptides calls for the peptide to contain 40-50% hydrophobic residues, usually aliphatic ones (I, L, V, A, M) (appropriately paired and mostly but not always alternating with polar residues in the sheet sequence), a positively charged (K, R) to negatively charged (E, D) residue ratio between 4/2 and 6/2, and a noncharged polar residue (N, Q, T, S) composition of about 20% or less. Results on four de novo designed, 33-residue peptides are presented supporting this approach. Under near physiologic conditions, all four peptides are soluble, form β-sheet structures to varying degrees, and self- associate. One peptide folds as a stable, compact β-sheet tetramer, whereas the others are transient β-sheet-containing aggregates.
AB - Based on observations of solubility and lording properties of peptide 33-mers derived from the β-sheet domains of platelet factor-4 (PF4), interleukin-8 (IL-8), and growth related protein (Gro-α), as well as other β-sheet-forming peptides, general guidelines have been developed to aid in the design of water soluble, self association-induced β-sheet-forming peptides. CD, 1H-NMR, and pulsed field gradient NMR self-diffusion measurements have been used to assess the degree of folding and state of aggregation. PF4 peptide forms native-like β-sheet tetramers and is sparingly soluble above pH 6. IL-8 peptide is insoluble between pH 4.5 and pH 7.5, yet forms stable, native-like β-sheet dimers at higher pH. Gro-α peptide is soluble at all pH values, yet displays no discernable β-sheet structure even when diffusion data indicate dimer tetramer aggregation. A recipe used in the de novo design of water-soluble β-sheet-forming peptides calls for the peptide to contain 40-50% hydrophobic residues, usually aliphatic ones (I, L, V, A, M) (appropriately paired and mostly but not always alternating with polar residues in the sheet sequence), a positively charged (K, R) to negatively charged (E, D) residue ratio between 4/2 and 6/2, and a noncharged polar residue (N, Q, T, S) composition of about 20% or less. Results on four de novo designed, 33-residue peptides are presented supporting this approach. Under near physiologic conditions, all four peptides are soluble, form β-sheet structures to varying degrees, and self- associate. One peptide folds as a stable, compact β-sheet tetramer, whereas the others are transient β-sheet-containing aggregates.
KW - CD
KW - NMR
KW - folding
KW - peptide
KW - self-association
KW - β-sheet structure
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U2 - 10.1002/pro.5560050709
DO - 10.1002/pro.5560050709
M3 - Article
C2 - 8819163
AN - SCOPUS:0029927321
SN - 0961-8368
VL - 5
SP - 1301
EP - 1315
JO - Protein Science
JF - Protein Science
IS - 7
ER -