Abstract:
:The magnitude and nature of lesion-induced energetic perturbations empirically correlate with mutagenicity/cytotoxicity profiles and can be predictive of lesion outcomes during polymerase-mediated replication in vitro. In this study, we assess the sequence and counterbase-dependent energetic impact of the Thymine glycol (Tg) lesion on a family of deoxyoligonucleotide duplexes. Tg damage arises from thymine and methyl-cytosine exposure to oxidizing agents or radiation-generated free-radicals. The Tg lesion blocks polymerase-mediated DNA replication in vitro and the unrepaired site elicits cytotoxic lethal consequences in vivo. Our combined calorimetric and spectroscopic characterization correlates Tg -induced energetic perturbations with biological and structural properties. Specifically, we incorporate a 5R-Tg isomer centered within the tridecanucleotide sequence 5'-GCGTACXCATGCG-3' (X = Tg or T) which is hybridized with the corresponding complementary sequence 5'-CGCATGNGTACGC-3' (N = A, G, T, C) to generate families of Tg -damaged (Tg ·N) and lesion-free (T·N) duplexes. We demonstrate that the magnitude and nature of the Tg destabilizing impact is dependent on counterbase identity (i.e., A ∼ G < T < C). The observation that a Tg lesion is less destabilizing when positioned opposite purines suggests that favorable counterbase stacking interactions may partially compensate lesion-induced perturbations. Moreover, the destabilizing energies of Tg ·N duplexes parallel their respective lesion-free T·N mismatch counterparts (i.e., G < T < C). Elucidation of Tg-induced destabilization relative to the corresponding undamaged mismatch energetics allows resolution of lesion-specific and sequence-dependent impacts. The Tg-induced energetic perturbations are consistent with its replication blocking properties and may serve as differential recognition elements for discrimination by the cellular repair machinery.
journal_name
Biopolymersjournal_title
Biopolymersauthors
Minetti CA,Remeta DP,Iden CR,Johnson F,Grollman AP,Breslauer KJdoi
10.1002/bip.22680subject
Has Abstractpub_date
2015-09-01 00:00:00pages
491-508issue
9eissn
0006-3525issn
1097-0282journal_volume
103pub_type
杂志文章相关文献
BIOPOLYMERS文献大全abstract::We have previously proposed a model for the delta-opioid receptor binding conformation of the high affinity tetrapeptide Tyr-c[D-Cys-Phe-D-Pen]OH (JOM-13) based on experimental and theoretical conformational analysis of this peptide and a correlation of conformational preferences of further conformationally restricted...
journal_title:Biopolymers
pub_type: 杂志文章
doi:10.1002/(sici)1097-0282(199609)39:3<287::aid-bip2>
更新日期:1996-09-01 00:00:00
abstract::The characterization of elastic properties of biopolymers is crucial to understand many molecular reactions determined by conformational bending fluctuations of the polymer. Direct measurement of such elastic properties using single-molecule methods is usually hindered by the intrinsic tendency of such biopolymers to ...
journal_title:Biopolymers
pub_type: 杂志文章
doi:10.1002/bip.22533
更新日期:2014-12-01 00:00:00
abstract::The large abundance of bioactive single- and multiple-stranded cystine-rich peptides in nature has fostered the development of orthogonal thiol-protection schemes and of efficient chemistries for regioselective disulfide formation in synthetic replica for decades. In parallel to these entirely synthetic strategies, an...
journal_title:Biopolymers
pub_type: 杂志文章,评审
doi:10.1002/bip.20174
更新日期:2005-01-01 00:00:00
abstract::Collagen is a natural protein, which is used as a vital biomaterial in tissue engineering. The major concern about native collagen is lack of its thermal stability and weak resistance to proteolytic degradation. In this scenario, the crosslinking compounds used for stabilization of collagen are mostly of chemical natu...
journal_title:Biopolymers
pub_type: 杂志文章
doi:10.1002/bip.22473
更新日期:2014-08-01 00:00:00
abstract::Amyloid aggregates have been implicated in the pathogenesis of diseases such as type 2 diabetes, Alzheimer's, Parkinson's, and prion disease. Recently determined microcrystal structures of several short peptide segments derived from fibril-forming proteins revealed coexistence of alternative aggregation modes (amyloid...
journal_title:Biopolymers
pub_type: 杂志文章
doi:10.1002/bip.21731
更新日期:2012-01-01 00:00:00
abstract::The hinge region links the antigen binding Fab part to the constant Fc domain in immunoglobulins. For the hinge peptide derivative [AcThr(OtBu)-Cys-Pro-Pro-Cys-Pro-Ala-ProNH2]2 the assignment of the 1H and 13C resonances was achieved by two-dimensional nmr techniques: total correlation spectroscopy (TOCSY), nuclear Ov...
journal_title:Biopolymers
pub_type: 杂志文章
doi:10.1002/bip.360311007
更新日期:1991-09-01 00:00:00
abstract::In the native structure of hen egg white lysozyme (HEL), the amino acid sequence 87-97 (HEL 87-97) forms an amphiphilic helix, with hydrophilic residues in the sequence directed toward the solvent. A synthetic version of the HEL 87-97 sequence (with the cysteine corresponding to position 94 of HEL replaced by alanine)...
journal_title:Biopolymers
pub_type: 杂志文章
doi:10.1002/bip.360330307
更新日期:1993-03-01 00:00:00
abstract::We applied dynamic light scattering technique on the model system of hen egg lysozyme in salt-free aqueous ethanol solution to study the mechanism of denaturation and aggregation of protein. At low ethanol concentration [0-63% (v/v)], the fast relaxation mode was observed, which was caused by lysozyme molecules in the...
journal_title:Biopolymers
pub_type: 杂志文章
doi:10.1002/1097-0282(20011015)59:5<370::AID-BIP1034>3
更新日期:2001-10-15 00:00:00
abstract::A secondary structure sequence is a symbolic string composed of three kinds of letters, indicating the helix, strand, and coil (including turns), respectively. A graphic representation for this abstract symbolic sequence is proposed here, called the S curve. The S curve is the unique representation for a given seconda...
journal_title:Biopolymers
pub_type: 杂志文章
doi:10.1002/(SICI)1097-0282(200006)53:7<539::AID-BIP2>
更新日期:2000-06-01 00:00:00
abstract::We present a method for analysis of a fitness landscape of a biopolymer with significantly epistatic sites. The analysis is based on a quasi-additive fitness model. The fitness model is constructed with additive terms conducted by "site-fitness" and epistatic terms conducted by "pair-fitness," where the site-fitness i...
journal_title:Biopolymers
pub_type: 杂志文章
doi:10.1002/bip.10126
更新日期:2002-07-05 00:00:00
abstract::Multiple, independent sites or domains behave, on chemical change, in a manner predicted by Langmuir. Distortions of this behavior have been attributed to interactions between the domains, which vary with the progress of the changes occurring at the sites or domains. The two main models for nearest neighbor interactio...
journal_title:Biopolymers
pub_type: 杂志文章
doi:10.1002/(SICI)1097-0282(199905)49:6<425::AID-BIP1>
更新日期:1999-05-01 00:00:00
abstract::The thermal conformational transitions of two sonicated samples of schizophyllan were studied in water-dimethylsulfoxide (DMSO) mixtures by high-sensitivity differential scanning calorimetry (DSC). Two transitions were observed over most of the range of solvent compositions. These were assigned to an internal change o...
journal_title:Biopolymers
pub_type: 杂志文章
doi:10.1002/bip.360280208
更新日期:1989-02-01 00:00:00
abstract::This report details the observation of (a) the intact double helix of DNA at 0% relative humidity in poly(dA).poly(dT) and poly(dA-dT).poly(dA-dT) films, (b) the fractal-like growth of DNA crystals in films of poly(dA).poly(dT), and (c) poly(dA).poly(dT) with adenines in the B form and thymines in the A form. Observat...
journal_title:Biopolymers
pub_type: 杂志文章
doi:10.1002/bip.360340814
更新日期:1994-08-01 00:00:00
abstract::The conformation and intermolecular association of [D-Hyi2, L-Hyi4] meso-valinomycin [cyclo[-D-Val-D-Hyi-L-Val-L-Hyi-(D-Val-L-Hyi-L-Val-D-+ ++Hyi)2-], C60H102N6O18] in a crystal form obtained from ethanol solution has been determined by x-ray crystallography. Two depsipeptides and one ethanol molecule per asymmetric u...
journal_title:Biopolymers
pub_type: 杂志文章
doi:10.1002/(SICI)1097-0282(199711)42:6<645::AID-BIP3>
更新日期:1997-11-01 00:00:00
abstract::The conformational study on Arg-Gly-Asp (RGD)-containing tetrapeptides in the unhydrated and hydrated states has been carried out using the force field ECEPP/3 and the hydration shell model. The tetrapeptides studied here are H-RGDX-OH (X = Trp, Tyr, Phe, Leu, Val, Cys, Gln, and Ser), which show the inhibitory activit...
journal_title:Biopolymers
pub_type: 杂志文章
doi:10.1002/bip.10067
更新日期:2002-04-15 00:00:00
abstract::The process of protein folding is obviously driven by forces exerted on the atoms of the amino-acid chain. These forces arise from interactions with other parts of the protein itself (direct forces), as well as from interactions with the solvent (solvent-induced forces). We present a statistical-mechanical formalism t...
journal_title:Biopolymers
pub_type: 杂志文章
doi:10.1002/bip.23020
更新日期:2017-08-01 00:00:00
abstract::Synthesis and CD and (13)C(alpha)-NMR studies in a near-neutral saline buffer are reported for a 65-residue peptide ((190)Tm(254)) comprising residues 190-254 of the alpha-tropomyosin chain. CD on a version disulfide cross-linked via the N-terminal cysteine side chains indicates that this dimer is highly helical and m...
journal_title:Biopolymers
pub_type: 杂志文章
doi:10.1002/1097-0282(20011005)59:4<257::AID-BIP1022>3
更新日期:2001-10-05 00:00:00
abstract::The phase content of amylose-water mixtures (0.7/0.3 w/w) has been analyzed by transmission Fourier transform infrared (FTIR) spectroscopy in the 1175-950 cm(-1) region. Spectra are obtained under three different conditions: (a) as a function of temperature (T) from 25 to 97 degrees C; (b) at room temperature (RT), af...
journal_title:Biopolymers
pub_type: 杂志文章
doi:10.1002/1097-0282(200103)58:3<305::AID-BIP1007>3.0
更新日期:2001-03-01 00:00:00
abstract::Hydrophobicity has proven to be an extremely useful parameter in small molecule drug discovery programmes given that it can be used as a predictive tool to enable rational design. For larger molecules, including peptoids, where folding is possible, the situation is more complicated and the average hydrophobicity (as d...
journal_title:Biopolymers
pub_type: 杂志文章
doi:10.1002/bip.23014
更新日期:2017-07-01 00:00:00
abstract::A three-dimensional model of DNA/RNA triple helix that contains a poly(L-deoxyadenosine) (L-dA) chain is proposed based on computer-assisted model building and energy calculations. The model building was performed by a new method that systematically searches possible conformations of nucleotide units in the helical ch...
journal_title:Biopolymers
pub_type: 杂志文章
doi:10.1002/bip.360321202
更新日期:1992-12-01 00:00:00
abstract::The constraints on combinations of nearest neighbors in nucleic acid sequences and the numbers of independent sequences needed to describe nearest-neighbor properties of oligomers and polymers are derived and summarized. It has been pointed out in previous work [D. M. Gray and I. Tinoco, Jr. (1970) Biopolymers, Vol. 9...
journal_title:Biopolymers
pub_type: 杂志文章
doi:10.1002/(sici)1097-0282(199712)42:7<783::aid-bip4>
更新日期:1997-12-01 00:00:00
abstract::alpha,beta-Dehydro amino acid residues are known to constrain the peptide backbone to the beta-bend conformation. A pentapeptide containing only one alpha,beta-dehydrophenylalanine (delta Phe) residue has been synthesized and crystallized, and its solid state conformation has been determined. The pentapeptide Boc-Leu-...
journal_title:Biopolymers
pub_type: 杂志文章
doi:10.1002/bip.360350202
更新日期:1995-02-01 00:00:00
abstract::Xylanase XYNII from Trichoderma longibrachiatum is a small protein of the molecular weight 21 kDa, belonging to the family 11 of glycosyl hydrolases, which catalyses hydrolysis of xylan. This article reports thermal stability study of xylanase XYN II conformation in the temperature range 15-65 degrees C by the small a...
journal_title:Biopolymers
pub_type: 杂志文章
doi:10.1002/bip.20605
更新日期:2006-12-15 00:00:00
abstract::Second-generation dendrimers have been prepared on solid phase by successive additions of branched polyproline building blocks starting from two different branching units anchored to the solid support. The preparation of Pro-rich building blocks was carried out by stepwise solid-phase synthesis and their iterative add...
journal_title:Biopolymers
pub_type: 杂志文章
doi:10.1002/bip.20125
更新日期:2004-01-01 00:00:00
abstract::Nodal, a member of the transforming growth factor-β superfamily, is a potent embryonic morphogen also implicated in tumor progression. Up to date structural information on the interaction of Nodal with its molecular partners are unknown. To deepen our understanding about mechanisms underlying both embryonic developmen...
journal_title:Biopolymers
pub_type: 杂志文章
doi:10.1002/bip.21517
更新日期:2010-11-01 00:00:00
abstract::The thermodynamics of the stacking to unstacking transitions of 24 single-stranded DNA sequences (ssDNA), 10-12 bases in length, in sodium phosphate buffer were determined from 10 to 95 degrees C, using differential scanning calorimetry (DSC). An additional 22 ssDNA sequences did not exhibit an S<=>U transition in thi...
journal_title:Biopolymers
pub_type: 杂志文章
doi:10.1002/bip.21044
更新日期:2008-11-01 00:00:00
abstract::The spatial variation in the composition of nonexpanded biopolymer blends prepared by extrusion of mixtures of gelatin with either native or pregelatinized waxy maize starch was studied using a 30-microm aperture FTIR microspectroscopy technique. The ratio of the areas of the "saccharide" bands (953-1180 cm(-1)) and t...
journal_title:Biopolymers
pub_type: 杂志文章
doi:10.1002/bip.1015
更新日期:2001-01-01 00:00:00
abstract::The creation of peptide libraries by site-selective modification of a few peptide substrates would increase the efficiency of discovery processes, but still is a real synthetic challenge. The site-selective modification of small peptides at serine or threonine residues, by using a short scission-addition procedure, al...
journal_title:Biopolymers
pub_type: 杂志文章
doi:10.1002/bip.22642
更新日期:2015-09-01 00:00:00
abstract::Ultraviolet hyperchromicity experiments indicate that in DNA duplex formation, a C-T mismatch is destabilizing in the center of a duplex, but behaves as a stable base pair at the terminus of a duplex. The C-T base pair is thought to contain two hydrogen bonds, but has thermodynamic parameters (delta Ho and delta Go of...
journal_title:Biopolymers
pub_type: 杂志文章
doi:10.1002/bip.360310908
更新日期:1991-08-01 00:00:00
abstract::Using high precision densimetric and ultrasonic measurements, we have determined, at 25 degrees C, the apparent molar volumes PhiV and the apparent molar compressibilities PhiK(S) of four nucleic acid duplexes-namely, the DNA duplex, poly(dIdC)poly(dIdC); the RNA duplex, poly(rA)poly(rU); and the two DNA/RNA hybrid du...
journal_title:Biopolymers
pub_type: 杂志文章
doi:10.1002/(SICI)1097-0282(19991015)50:5<459::AID-BIP
更新日期:1999-10-15 00:00:00