Home About us Contact
|
Home About us Contact | ||
|
|
||
One Residue (one + residue)
Selected AbstractsCapillary electrophoresis of amphipathic ,-helical peptide diastereomersELECTROPHORESIS, Issue 1 2004Traian V. Popa Abstract We have made a rigorous assessment of the ability of capillary electrophoresis to resolve peptide diastereomers through its application to the separation of a series of synthetic 18-residue, amphipathic ,-helical monomeric peptide analogues, where a single site in the centre of the hydrophobic face of the ,-helix is substituted by 19 L - or D -amino acids. Such L - and D -peptide pairs have the same mass-to-charge ratio, amino acid sequence and intrinsic hydrophobicity, varying only in the stereochemistry of one residue. CE approaches assessed in their ability to separate diastereomeric peptide pairs included capillary zone electrophoresis (uncoated capillary), micellar electrokinetic chromatography (uncoated capillary in the presence of 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate, CHAPS), open-tubular capillary electrochromatography (C8 -coated capillary in the presence of 25% 2,2,2-trifluoroethanol (TFE) or 25% ethanol). Overall, the OT-CEC methods were the most effective at separating the most peptide pairs, particularly for those containing hydrophilic side chains. However, the MEKC approach proved most effective for separation of peptide pairs containing hydrophobic or aromatic side chains. [source] Etiopathogenic role of HLA-B27 alleles in ankylosing spondylitisINTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 3 2005Nurullah AKKOC Abstract HLA-B27 is the major genetic susceptibility factor for ankylosing spondylitis (AS). However, its precise role in the pathogenesis of AS still remains unclear, even though its gene has been cloned and sequenced, and its crystallographic structure has been defined. Arthritogenic peptide and molecular mimicry hypotheses propose mechanisms related to an antigen-presenting function of HLA-B27 to be responsible for disease development. However, peculiar aspects of its immunobiology, such as its misfolding and heavy chain dimerization raise the possibility of involvement of pathogenic mechanisms unrelated to its physiological function. Moreover, HLA-B27 is not a single allele, but a family of 31 different alleles, named HLA-B*2701 to HLA-B*2727. Studies worldwide indicate that the relatively common alleles (subtypes) HLA-B*2705, B*2704, and B*2702 are strongly associated with AS, whereas HLA-B*2706 which is prevalent in South-east Asia and HLA-B*2709 which is prevalent on the Italian island of Sardinia, seem to lack such an association. The distinction between the disease-associated subtypes and those that are not associated, may provide clues to the actual role of HLA-B27 in disease pathogenesis. B*2706 differs from B*2704 by only two residues, and B*2709 differs from B*2705 by only one residue. Moreover, both B*2706 and B*2709 bind an endogenous peptide (derived from vasoactive intestinal peptide type 1 receptor) and also an exogenous peptide (latent membrane protein 2 of Epstein-Barr virus) but in two drastically diverse conformations. These recent X-ray diffraction studies of individual peptides in the context of different HLA-B27 alleles broaden our perception of the possible pathogenetic role of this molecule in the development of AS and related spondyloarthopathies. In summary, the pathogenetic role of HLA-B27 in AS seem to be quite heterogenous, and cannot be explained by a single mechanism, and new ideas have been raised based on the aberrant immunobiologic features of HLA-B27. [source] Structural effects of amino acid variations between B and CRF02-AG HIV-1 integrasesJOURNAL OF MEDICAL VIROLOGY, Issue 5 2008Isabelle Malet Abstract HIV-1 integrase is one of the three essential enzyme required for viral replication and has a great potential as a novel target for anti-HIV drugs. The sequence variability of the entire integrase (IN) was examined in HIV-1 subtype B and CRF02-AG antiretroviral naïve infected patients for the presence of naturally occurring polymorphisms IN gene sequences and protein structures from both subtypes were compared. The phylogenetic analysis showed a total concordance between the 3 pol gene sequences for patients identified as subtype B whereas 3% of patients identified as CRF02-AG showed a mixture of subtypes. The analysis of IN aa sequences showed that 13 positions (K/R14, V/I31, L/I101, T/V112, T/A124, T/A125, G/N134, I/V135, K/T136, V/I201, T/S206, L/I234, and S/G283) differed between subtypes B and CRF02-AG. As observed in the 3D model of the preintegration complex, these differences may impact the functional property of IN. The fact that most variations were grouped suggests that some of them are linked together through compensatory mechanisms. This comparison allowed us to identify several variations of amino acids in HIV-1 IN subtype CRF02-AG that could have a putative impact on anti-integrase sensitivity. In particular, the region formed by Thr125, Thr124, Val31 contains at least one residue, T125, which variation has been involved in eliciting resistance to the naphtyridine carboxamide L870,810 IN inhibitor. In conclusion, virological response to anti-integrase should be studied carefully, according to the subtype, in clinical trials. J. Med. Virol. 80:754,761, 2008. © 2008 Wiley-Liss, Inc. [source] Negative ion dissociation of peptides containing hydroxyl side chainsRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 2 2008Dan Pu The dissociation of deprotonated peptides containing hydroxyl side chains was studied by electrospray ionization coupled with Fourier transform ion cyclotron resonance (ESI-FTICR) via sustained off-resonance irradiation collision induced dissociation (SORI-CID). Dissociation under post-source decay (PSD) conditions was performed by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF). This work included hexapeptides with one residue of serine, threonine, or tyrosine and five inert alanine residues. During SORI-CID and PSD, dissociation of [M,H], yielded c- and y-ions. Side-chain losses of formaldehyde (HCHO) from serine-containing peptides, acetaldehyde (CH3CHO) from threonine-containing peptides, and 4-methylene-2,5-cycohexadienone (C7H6O) from tyrosine-containing peptides were generally observed in the negative ion PSD and SORI-CID spectra. Side-chain loss occurs much less from tyrosine-containing peptides than from serine- and threonine-containing peptides. This is probably due to the bulky side chain of tyrosine, resulting in steric hindrance and poor geometry for dissociation reactions. Additionally, a selective cleavage leading to the elimination of the C-terminal residue from [M,H], was observed from the peptides with serine and threonine at the C-terminus. This cleavage does not occur in the dissociation of peptides with an amide group at the C-terminus or peptides with neutral or basic residues at the C-terminus. It also does not occur with tyrosine at the C-terminus. Both the C-terminal carboxylic acid group and the hydroxyl side chain of the C-terminal residue must play important roles in the mechanism of C-terminal residue loss. A mechanism involving both the C-terminal carboxylic acid group and a hydroxyl side chain of serine and threonine is proposed. Copyright © 2007 John Wiley & Sons, Ltd. [source] Application of NMR, molecular simulation, and hydrodynamics to conformational analysis of trisaccharides,BIOPOLYMERS, Issue 4 2003Ann M. Dixon Abstract The preferred conformations and conformational flexibilities of the trisaccharides ,-D-Glcp -(1,2)-,-D-Glcp -(1,3)-,-D-Glcp -OMe (I) and ,-D-Glcp -(1,3)[,-D-Glcp -(1,4)]-,-D-Glcp -OMe (II) in aqueous solution were determined using nuclear magnetic resonance (NMR) spectroscopy, molecular dynamics (MD) and Langevin dynamics (LD) simulations, and hydrodynamics calculations. Both trisaccharides have a vicinal substitution pattern in which long range (nonsequential) interactions may play an important role. LD simulation at 600 K indicated that the all- syn conformation predominated, though other conformations were apparent. NOE data and MD and LD simulations at 298 K all indicated that trisaccharide I is a single all- syn conformer in solution. Given that previous studies showed evidence of anti -conformers in ,-D-Glcp -(1,2)-,-D-Glcp -(1,3)-,-D-Glcp -OMe, this result provides an example of how changing the anomeric configuration of one residue from , to , can make an oligosaccharide more rigid. Discrepancies in inter-ring distances obtained by experiment and by simulation of the all- syn conformer suggest the presence of an anti -, conformation at the ,-(1,4)-linkage for II. A combined analysis of measured and calculated translational diffusion constants and 13C T1 relaxation times yield order parameters of 0.9 for each trisaccharide. This implies that any interconversion among conformations is significantly slower than tumbling. Anisotropies of approximately 1.6 and 1.3 calculated for I and II, respectively, are consistent with the observed relatively flat T1 profiles because the tumbling is not in the motional narrowing regime. Published 2003 Wiley Periodicals, Inc. Biopolymers 69: 448,460, 2003 [source] | |||||||||||||