Linked Life Data

16834392

Source:http://linkedlifedata.com/resource/pubmed/id/16834392

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
28
pubmed:dateCreated
2006-7-12
pubmed:abstractText
The design, synthesis, and characterization of a folded high-affinity metal-binding peptide is described. Based on the previously described folded peptide NTH-18, in which an alpha-helix was constrained through two disulfide bonds to a C-terminal extension of noncanonical secondary structure, a peptide (1) was designed to contain two histidine residues in positions 3 and 7. Air oxidation of 1 led to the formation of peptide 2, which contained two intramolecular disulfide bonds. The presence of the two histidines significantly destabilized the alpha-helical structure of 2 when compared to NTH-18. However, CD spectroscopy revealed that the addition of certain transition metal ions allowed the reformation of a stable alpha-helix. CD, NMR, and EPR spectroscopy as well as MALDI-TOF mass spectrometry indicated that 2 bound to Cu2+ to form a 1:1 complex via the imidazoles of the two histidine side chains. A glycine displacement assay revealed a dissociation constant for this complex of 5 nM at pH 8, which is the lowest reported value for a designed Cu2+-binding peptide. This peptide displayed more than 100-fold selectivity for Cu2+ over Zn2+, Ni2+, and Co2+. The 1.05 A crystal structure of the Cu(II)-complex of 2 revealed a square-pyramidal coordination geometry and confirmed that 2 bound to copper in an alpha-helical conformation via its two histidine side chains. The high affinity metal binding of peptide 2 demonstrates that metals can be used for the selective nucleation of alpha-helices.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0002-7863
pubmed:author
pubmed:issnType
Print
pubmed:day
19
pubmed:volume
128
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
9187-93
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Designed high affinity Cu2+-binding alpha-helical foldamer.
pubmed:affiliation
School of Chemistry, Cardiff University, Main Building, Park Place, Cardiff, CF10 3AT, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't