抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Theoretical descriptions of two-dimensional (2D) vibrational and electronic spectroscopy are presented By using a coupled multi-chromophore model, some examples of 2D spectroscopic studies of peptide solution structure determination and excitation transfer process in electronically coupled multi-chromophore system are discussed A few remarks on perspectives of this research area are given

Coherent Two-Dimensional Optical Spectroscopy

Medicinal attributes of 1,2,3-triazoles: Current developments

We investigated the polymer−water interaction in a model fibrous protein. Bombyx mori silk fibroin film, a typical model of biodegradable material, was cast from aqueous solution and analyzed in this study. Differential scanning calorimetry (DSC), its temperature-modulated variant (TMDSC), and the time-resolved technique of Fourier transform infrared spectroscopy (FTIR) were used for the first time to monitor the detailed structural changes of silk fibroin during heating and during isothermal crystallization above the glass transition temperature, Tg ∼ 451 K (178 °C). Results show that intermolecular bound water molecules, acting as a plasticizer, will strongly affect the secondary structure of silk fibroin. DSC study shows that silk fibroin initially displays a water-induced glass transition around 80 °C during heating, resulting from a temporary bound water-silk structure. Quantitative thermal analysis of the heat capacity changes of this system during heating revealed that no β-sheet crystals were form...

Dynamic Protein−Water Relationships during β-Sheet Formation

The ruthenium-catalyzed azide alkyne cycloaddition (RuAAC) affords 1,5-disubstituted 1,2,3-triazoles in one step and complements the more established copper-catalyzed reaction providing the 1,4-isomer. The RuAAC reaction has quickly found its way into the organic chemistry toolbox and found applications in many different areas, such as medicinal chemistry, polymer synthesis, organocatalysis, supramolecular chemistry, and the construction of electronic devices. This Review discusses the mechanism, scope, and applications of the RuAAC reaction, covering the literature from the last 10 years.

https://research.chalmers.se/publication/246752/file/246752_Fulltext.pdf

Ruthenium-Catalyzed Azide Alkyne Cycloaddition Reaction: Scope, Mechanism, and Applications.

The effect of hydrogen bonding on the amide group vibrational spectra has traditionally been rationalized by invoking a resonance model where hydrogen bonding impacts the amide functional group by stabilizing its [(-)O-C=NH (+)] structure over the [O=C-NH] structure. However, Triggs and Valentini's UV-Raman study of solvation and hydrogen bonding effects on epsilon-caprolactum, N, N-dimethylacetamide (DMA), and N-methylacetamide (NMA) ( Triggs, N. E.; Valentini, J. J. J. Phys. Chem. 1992, 96, 6922-6931) casts doubt on the validity of this model by demonstrating that, contrary to the resonance model prediction, carbonyl hydrogen bonding does not impact the AmII' frequency of DMA. In this study, we utilize density functional theory (DFT) calculations to examine the impact of hydrogen bonding on the C=O and N-H functional groups of NMA, which is typically used as a simple model of the peptide bond. Our calculations indicate that, as expected, the hydrogen bonding frequency dependence of the AmI vibration predominantly derives from the C=O group, whereas the hydrogen bonding frequency dependence of the AmII vibration primarily derives from N-H hydrogen bonding. In contrast, the hydrogen bonding dependence of the conformation-sensitive AmIII band derives equally from both C=O and N-H groups and thus, is equally responsive to hydrogen bonding at the C=O or N-H site. Our work shows that a clear understanding of the normal mode composition of the amide vibrations is crucial for an accurate interpretation of the hydrogen bonding dependence of amide vibrational frequencies.

Dependence of amide vibrations on hydrogen bonding.

We used UV resonance Raman (UVRR) spectroscopy to quantitatively correlate the peptide bond AmIII3 frequency to its Ψ Ramachandran angle and to the number and types of amide hydrogen bonds at different temperatures. This information allows us to develop a family of relationships to directly estimate the Ψ Ramachandran angle from measured UVRR AmIII3 frequencies for peptide bonds (PBs) with known hydrogen bonding (HB). These relationships ignore the more modest Φ Ramachandran angle dependence and allow determination of the Ψ angle with a standard error of ±8°, if the HB state of a PB is known. This is normally the case if a known secondary structure motif is studied. Further, if the HB state of a PB in water is unknown, the extreme alterations in such a state could additionally bias the Ψ angle by ±6°. The resulting ability to measure Ψ spectroscopically will enable new incisive protein conformational studies, especially in the field of protein folding. This is because any attempt to understand reaction me...

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Peptide Secondary Structure Folding Reaction Coordinate: Correlation between UV Raman Amide III Frequency, Ψ Ramachandran Angle, and Hydrogen Bonding

UV resonance Raman (UVR) spectroscopy was used to examine the solution conformation of poly-l-lysine (PLL) and poly-l-glutamic acid (PGA) in their non-alpha-helical states. UVR measurements indicate that PLL (at pH = 2) and PGA (at pH = 9) exist mainly in a mixture of polyproline II (PPII) and a novel left-handed 2.5(1)-helical conformation, which is an extended beta-strand-like conformation with Psi approximately +170 degrees and Phi approximately -130 degrees . Both of these conformations are highly exposed to water. The energies of these conformations are very similar. We see no evidence of any disordered "random coil" states. In addition, we find that a PLL and PGA mixture at neutral pH is approximately 60% beta-sheet and contains PPII and extended 2.5(1)-helix conformations. The beta-sheet conformation shows little evidence of amide backbone hydrogen bonding to water. We also developed a method to estimate the distribution of Psi Ramachandran angles for these conformations, which we used to estimate a Psi Ramachandran angle energy landscape. We believe that these are the first experimental studies to give direct information on protein and peptide energy landscapes.

UV resonance Raman determination of polyproline II, extended 2.5(1)-helix, and beta-sheet Psi angle energy landscape in poly-L-lysine and poly-L-glutamic acid.

3′-Azidothymidine (AZT) was the first approved antiviral for the treatment of human immunodeficiency virus (HIV). Reported efforts in clicking the 3′-azido group of AZT have not yielded 1,2,3-triazoles active against HIV or any other viruses. We report herein the first AZT-derived 1,2,3-triazoles with submicromolar potencies against HIV-1. The observed antiviral activities from the cytopathic effect (CPE) based assay were confirmed through a single replication cycle assay. Structure–activity-relationship (SAR) studies revealed two structural features key to antiviral activity: a bulky aromatic ring and the 1,5-substitution pattern on the triazole. Biochemical analysis of the corresponding triphosphates showed lower ATP-mediated nucleotide excision efficiency compared to AZT, which along with molecular modeling suggests a mechanism of preferred translocation of triazoles into the P-site of HIV reverse transcriptase (RT). This mechanism is corroborated with the observed reduction of fold resistance of the t...

Clicking 3′-Azidothymidine into Novel Potent Inhibitors of Human Immunodeficiency Virus

Neutral trialanine (Ala3), which is geometrically constrained to have its peptide bond at Φ and Ψ angles of α-helix and PPII-like conformers, are studied at the B3LYP/6-31+G(d,p) level of theory to...

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Nataliya S. Myshakina

Papers

Dependence of amide vibrations on hydrogen bonding.

Peptide Secondary Structure Folding Reaction Coordinate: Correlation between UV Raman Amide III Frequency, Ψ Ramachandran Angle, and Hydrogen Bonding

UV resonance Raman determination of polyproline II, extended 2.5(1)-helix, and beta-sheet Psi angle energy landscape in poly-L-lysine and poly-L-glutamic acid.

Clicking 3′-Azidothymidine into Novel Potent Inhibitors of Human Immunodeficiency Virus

Peptide bond vibrational coupling.