Biomedical subjects

Q H Dai

Publications and source records attributed to Q H Dai.

6 recordsLinked to original sources

PubMed2000

Site-specific NMR monitoring of cis-trans isomerization in the folding of the proline-rich collagen triple helix.

Understanding the folding of the proline-rich collagen triple helix requires consideration of the effects of proline cis-trans isomerization and may shed light on the misfolding of collagen in connective tissue diseases. Folding was monitored in real time by heteronuclear 2D NMR spectroscopy for the (15)N labeled positions in the triple-helical peptide T1-892 [GPAGPAGPVGPAGARGPAGPOGPOGPOGPOGV]. In the equilibrium unfolded monomer form, each labeled residue showed multiple peaks with interconversion rates consistent with cis-trans isomerization of Gly-Pro and Pro-Hyp bonds. Real-time NMR studies on the folding of T1-892 showed slow decay of monomer peaks and a concomitant increase in trimer peaks. Gly25 in the C-terminal rich (Gly-Pro-Hyp)(4) domain folds first, consistent with its being a nucleation domain. Analysis of the kinetics indicates that the folding of Gly25 is biphasic and the slower step represents cis-trans isomerization of imino acids. This illustrates that nucleation is limited by cis-trans isomerization. Monitoring Gly6, Gly10, Ala12, and Gly13 monomer and trimer peaks captures the C- to N-terminal propagation of the triple helix, which is also limited by Gly-Pro cis-trans isomerization events. The zipper-like nature of the propagation process is confirmed by the slower rate of folding of Ala6 compared to Gly13, reflecting the larger number of isomerization events encountered by the more N-terminal Ala6. The cis-trans isomerization events at multiple proline residues is a complex statistical process which can be visualized by these NMR studies.

Amino Acid Sequence↗

PubMed2000

Identification of Ehrlichia chaffeensis by nested PCR in ticks from Southern China.

A total of 717 ticks collected from southern China were examined by nested PCR for the presence of Ehrlichia chaffeensis. Sixteen (55. 2%) of 29 adult Amblyomma testudinarium ticks and 28 (11.7%) of 240 adult and at least 4.2% of 215 nymphal (pooled specimens) Haemaphysalis yeni ticks tested positive. Four other species of ticks were negative. Selected positive amplicons were confirmed by DNA sequencing.

Animals↗

PubMed1998

Nuclear magnetic resonance shows asymmetric loss of triple helix in peptides modeling a collagen mutation in brittle bone disease.

To investigate a human folding disease, NMR studies were carried out on collagen-like peptides to define the structural consequences of a single amino acid change found in patients with osteogenesis imperfecta (OI), a disease characterized by fragile bones. One peptide included a normal collagen sequence, while a second peptide included a Gly --> Ser substitution as found in a nonlethal case of OI. Residue specific internal dynamics and conformational studies indicate that the normal collagen-like sequence forms a triple helix which is rigid along its entire length. The introduction of a Gly --> Ser substitution induces an asymmetric disruption of the uniform triple helix. While the C-terminal end of the peptide retains the triple helix, the Ser substitution site and residues N-terminal to it exhibit the mobility of a random chain. This equilibrium state indicates that a Gly substitution can terminate the C to N propagation of the triple helix and suggests that renucleation is required for folding to continue. Defective folding has been implicated in brittle bone disease, and these results begin to characterize the folding process in OI collagens. OI collagen studies may also provide insights about defective protein folding, assembly, and aggregation in other human diseases.

Amino Acid Sequence↗

PubMed1991

Quantitative explanation on structure-carcinogenic activity relationship of aromatic amines by di-region theory.

Di-region theory, the theory for the mechanism of carcinogenesis, has been extended successfully on the quantitative structure-carcinogenic activity relationship (QSCAR) of 63 aromatic amines. A quantitative equation for the QSCAR of aromatic amines has been established by the mechanism conception of the specialized di-functional alkylation between the nitrenium ion of the amino group and the epoxide of the aromatic ring. The agreement between calculation and experiment comes up to 98%. Thus, it can now express the puzzling variation of the carcinogenicity of aromatic amines, as a comprehensible structure-chemical reactivity relationship.

2-Acetylaminofluorene↗

PubMed1989

Quantitative pattern recognition for structure-carcinogenic activity relationship of N-nitroso compounds based upon Di-region theory.

In this paper, it is evidenced by the quantitative structure-carcinogenic activity relationship (QSCAR) and the pattern recognition treatment of N-nitroso compounds (NNC) that the key step of carcinogenesis induced by NNC is the cross-linking on the complementary base pair of DNA, through the bifunctional alkylation between alpha-carbon and another carbon within the same chain. The alkylation by the alpha-carbon atom is through the diazonium salt, but that by the atom other than the alpha-position is through the active ester formed from the hydroxylated metabolite of the chain. Therefore, the alkylation by the beta-position of NNC, or by its gamma-position, under suitable conditions, of which the distances from the alpha-position both approach 2.80-3.00 A, would be the most favourable positions along with the alpha-position for the cross-linking to occur between the complementary base pairs of DNA, which will yield the carcinogenic activity of NNC. The above conception of bifunctional alkylation can reduce the QSCAR of NNC to a reasonable structure-chemical reactivity relationship under the complex biological conditions, and is the successful extension of the Di-region theory to the carcinogenesis mechanism of the important NNC series. In the light of the above viewpoint, for 153 NNCs including the nitrosamines and nitrosamides which have been tested reliably with animals, the correct discrimination ratio by quantitative pattern recognition according to carcinogenic activity indexes divided into 5 degrees comes up to as high as 97%.

Alkylation↗

PubMed1985

Quantitative structure-carcinogenic activity relationship of methyl, alkyl, cyclopentano, cyclohexano polycyclic aromatic hydrocarbons and cholanthrene series.

By applying the di-region theory, in this paper, the quantitative structure-carcinogenic activity relationship of methyl, alkyl, cyclopentano, cyclohexano polycyclic aromatic hydrocarbons (PAH) and cholanthrene series totalling 187 alkyl-substituted PAH compounds is established reasonably and systematically for the first time. The consistent ratio between calculation and experiment is more than 95%. In the metabolic course of methyl PAH, which one is the so-called "ultimate carcinogen", the bay-region carbonium ion situated on the angular ring or methylene carbonium ion produced from the methyl group, is still in dispute at present. Now, the afore-mentioned disputable viewpoints have been successfully integrated by the di-region theory.

Animals↗