Electronic control of peptide cis-trans isomerism

ORGN 730

Neal J. Zondlo, Krista M. Thomas, and Alaina M. Brown. Department of Chemistry and Biochemistry, University of Delaware, 206 Lammot DuPont Laboratories, Newark, DE 19716
Polyproline helix (PPII) is a major conformation in protein-protein interfaces and has been proposed as a dominant conformation in proline-rich domains. We synthesized and analyzed a series of model peptides (Ac-GPPXPPGY-NH2) to experimentally determine the propensities of amino acids for PPII. We found proline and leucine to most strongly favor PPII. Three classes of residues disfavored PPII: beta-branched residues, residues with short polar sidechains, and aromatic residues. NMR revealed that the basis of low PPII propensity for aromatic residues was amide cis-trans isomerism, with aromatic residues displaying high percentages (30-60%) of species with cis amide bonds. We synthesized a series of peptides with electron-rich and electron-poor aromatic residues preceding proline. We find, in proline-rich peptides and model tetrapeptides, that electron-poor residues preceding proline display little cis amide conformation and support PPII, whereas more electron-rich aromatic residues strongly favor cis amide bond formation and can support type VI beta turn formation.
 

Proteins, Peptides, and Amino Acids
8:00 AM-12:00 PM, Thursday, August 26, 2004 Pennsylvania Convention Center -- 201A, Oral

Division of Organic Chemistry

The 228th ACS National Meeting, in Philadelphia, PA, August 22-26, 2004