Migration on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) that does not correlate with formula molecular weights, termed "gel shifting," appears to be common for membrane proteins but has yet conclusively explained. In the present work, we investigate anomalous mobility of helical using a library wild-type and mutant helix-loop-helix ("hairpin") sequences derived from transmembrane segments 3 4 human cystic fibrosis conductance regulator (CFTR), including...

Cationic antimicrobial peptides (CAPs) occur as important innate immunity agents in many organisms, including humans, and offer a viable alternative to conventional antibiotics, they physically disrupt the bacterial membranes, leading membrane lysis eventually cell death. In this work, we studied biophysical microbiological characteristics of designed CAPs varying hydrophobicity levels charge distributions by variety biochemical approaches, in-tandem atomic force microscopy, attenuated total...

In a survey of the bilayer-spanning regions integral membrane proteins, membrane-buried proline residues were found in nearly all transport proteins examined, whereas nontransport largely devoid intramembranous residues. When amino acids from complete sequences representative sets and analyzed for distribution between aqueous vs. membranous domains, was shown to be selectively excluded domains accord with expectation energetic structural considerations. contrast, evenly distributed...

Proline is established as a potent breaker of both alpha-helical and beta-sheet structures in soluble (globular) proteins. Thus, the frequent occurrence Pro residue putative transmembrane helices integral membrane proteins, particularly transport presents structural dilemma. We propose that this phenomenon results from fact propensity given amino acid may be altered to conform changes imposed by molecular environment. To test hypothesis on proline, we synthesized model peptides generic...

Novel cationic antimicrobial peptides typified by structures such as KKKKKKAAXAAWAAXAA-NH2, where X = Phe/Trp, and several of their analogues display high activity against a variety bacteria but exhibit no hemolytic even at dose levels in mammalian erythrocytes. To elucidate mechanism action source selectivity for bacterial membranes, phospholipid mixtures mimicking the compositions natural membranes (containing anionic lipids) zwitterionic lipids + cholesterol) were challenged with...

The MICs of cationic, hydrophobic peptides the prototypic sequence KKAAAXAAAAAXAAWAAXAAAKKKK-amide (where X is one 20 commonly occurring amino acids) are in a low micromolar range for panel gram-negative and gram-positive bacteria, with no or hemolytic activity against human rabbit erythrocytes. active only when average segmental hydrophobicity 19-residue core above an experimentally determined threshold value Phe, Trp, Leu, Ile, Met, Val, Cys, Ala). Antimicrobial could be increased by using...

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNuclear magnetic resonance evidence for cis-peptide bonds in proline oligomersC. M. Deber, F. A. Bovey, J. P. Carver, and Elkan R. BloutCite this: Am. Chem. Soc. 1970, 92, 21, 6191–6198Publication Date (Print):October 1, 1970Publication History Published online1 May 2002Published inissue 1 October 1970https://pubs.acs.org/doi/10.1021/ja00724a016https://doi.org/10.1021/ja00724a016research-articleACS PublicationsRequest reuse permissionsArticle...

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTWhy cyclic peptides? Complementary approaches to conformationsCharles M. Deber, Vincent Madison, and Elkan R. BloutCite this: Acc. Chem. Res. 1976, 9, 3, 106–113Publication Date (Print):March 1, 1976Publication History Published online1 May 2002Published inissue 1 March 1976https://pubs.acs.org/doi/10.1021/ar50099a005https://doi.org/10.1021/ar50099a005research-articleACS PublicationsRequest reuse permissionsArticle...

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTConformations of (X-L-Pro-Y)2 cyclic hexapeptides. Preferred .beta.-turn conformers and implications for .beta. turns in proteinsLila M. Gierasch, Charles Deber, Vincent Madison, Chien-Hua Niu, Elkan R. BloutCite this: Biochemistry 1981, 20, 16, 4730–4738Publication Date (Print):August 1, 1981Publication History Published online1 May 2002Published inissue 1 August...

Significance Using D-amino acids as the building blocks for bioactive peptides can dramatically increase their potency. However, simply swapping regular levorotary amino dextrorotary (D)-amino alters peptide surface topology and function is lost. Current methods to overcome this are not generally applicable exclude majority of therapeutic targets. By creating a mirror image all 111,867 protein structures in Protein Data Bank (PDB), we convert repository into D-peptide database with 2.8...

Abstract The outer membrane (OM) is a hallmark feature of gram-negative bacteria that provides the species with heightened resistance against antibiotic threats while cationic antimicrobial peptides (CAPs) are natural antibiotics broadly recognized for their ability to disrupt bacterial membranes. It has been well-established lipopolysaccharides present on OM among major targets CAP activity species. Here we investigate how relative distribution charged residues along primary peptide...

Abstract Based on the principle of dual prediction by segment hydrophobicity and nonpolar phase helicity, in concert with imposed threshold values these two parameters, we developed automated program TM Finder that can successfully locate most transmembrane (TM) segments proteins. The uses results experiments a series host‐guest mimic peptides prototypic sequence KK AAA X AAAAA AAWAA KKKK‐amide (where = each 20 commonly occurring amino acids) through which an HPLC‐derived hydropathy scale,...

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCyclic peptides. IX. Conformations of a synthetic ion-binding cyclic peptide, cyclo-(Pro-Gly)3, from circular dichroism and proton carbon-13 nuclear magnetic resonanceV. Madison, M. Atreyi, C. Deber, E. R. BloutCite this: J. Am. Chem. Soc. 1974, 96, 21, 6725–6734Publication Date (Print):October 1, 1974Publication History Published online1 May 2002Published inissue 1 October...

An inherent dilemma in the study of structural biology membrane proteins is that it often necessary to use detergents mimic native lipid bilayer environment. This situation particular interest because generation high-resolution structures (through X-ray crystallography and solution NMR) has overwhelmingly relied upon identification which may be solubilized without denaturation into a nonbiological state. While sodium dodecyl sulfate (SDS) perhaps most widely employed micelle-forming...

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTInfluence of ether linkage on the lamellar to hexagonal phase transition ethanolamine phospholipidsJ. M. Boggs, D. Stamp, W. Hughes, and C. DeberCite this: Biochemistry 1981, 20, 5728–5735Publication Date (Print):September 29, 1981Publication History Published online1 May 2002Published inissue 29 September 1981https://pubs.acs.org/doi/10.1021/bi00523a015https://doi.org/10.1021/bi00523a015research-articleACS PublicationsRequest reuse...

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCyclic peptides. I. Cyclo(tri-L-prolyl) and derivatives. Synthesis molecular conformation from nuclear magnetic resonanceElkan R. Blout, Charles M. Deber, Dennis A. TorchiaCite this: J. Am. Chem. Soc. 1971, 93, 19, 4893–4897Publication Date (Print):September 1, 1971Publication History Published online1 May 2002Published inissue 1 September 1971https://pubs.acs.org/doi/10.1021/ja00748a038https://doi.org/10.1021/ja00748a038research-articleACS...

Abstract β‐ρ‐Nitrobenzyl‐ L ‐aspartate and γ‐ p ‐nitrobenzyl‐ ‐glutamate were synthesized, copolymers prepared respectively with β‐benzyl‐ D ‐(and ‐ ‐) aspartate γ‐benzyl‐ ‐glutamate. In chloroform there is a reversal in helical sense of poly‐β‐benzyl‐ to the right‐handed poly‐β‐ when 26–32 mole‐% latter present copolymer. A new conformationally dependent Cotton effect was found for these at 370 mμ. dimethylformamide transition from random conformation ‐(or ‐aspartate. The formation side...

Natural α-helical cationic antimicrobial peptide (CAP) sequences are predominantly amphipathic, with only ca. 2% containing four or more consecutive positively charged amino acids (Lys/Arg). We have designed synthetic CAPs that deviate from these natural sequences, as typified by the charge-clustered KKKKKKAAFAAWAAFAA-NH2, (termed 6K-F17), which displays high activity no toxicity to mammalian cells. created a series of peptides varying in charge patterning, increasing amphipathic character...