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

https://pubs.rsc.org/en/content/articlepdf/2019/NP/C8NP00092A

Marine natural products.

https://chemistry.mdma.ch/hiveboard/rhodium/pdf/archive/merbst/quinoline1999.pdf

Quinoline, quinazoline and acridone alkaloids

Oxygen derived species such as superoxide radical, hydrogen peroxide, singlet oxygen and hydroxyl radical are well known to be cytotoxic and have been implicated in the etiology of a wide array of human diseases, including cancer. Various carcinogens may also partly exert their effect by generating reactive oxygen species (ROS) during their metabolism. Oxidative damage to cellular DNA can lead to mutations and may, therefore, play an important role in the initiation and progression of multistage carcinogenesis. The changes in DNA such as base modification, rearrangement of DNA sequence, miscoding of DNA lesion, gene duplication and the activation of oncogenes may be involved in the initiation of various cancers. Elevated levels of ROS and down regulation of ROS scavengers and antioxidant enzymes are associated with various human diseases including various cancers. ROS are also implicated in diabtes and neurodegenerative diseases. ROS influences central cellular processes such as proliferation a, apoptosis, senescence which are implicated in the development of cancer. Understanding the role of ROS as key mediators in signaling cascades may provide various opportunities for pharmacological intervention.

/pdf/reactive-oxygen-species-role-in-the-development-of-cancer-2rx5uwxcgy.pdf

Reactive oxygen species: role in the development of cancer and various chronic conditions

Polycyclic Hydrocarbons Vol. 1. Pp. xxvi + 487. 126S. (With a chapter on carcinogenesis by Regina Schoental.) Vol. 2. Pp. lvii + 487. 140s. By E. Clar. (London and New York: Academic Press; Berlin: Springer-Verlag, 1964.)

Polycyclic Aromatic Hydrocarbons

Vancomycin: structure and transformation to CDP-I

A G to T mutation has been observed at the third position of codon 249 of the p53 tumor-suppressor gene in over 50% of the hepatocellular carcinoma cases associated with high exposure to aflatoxin B1 (AFB1) Hypotheses have been put forth that AFB1, in concert with hepatitis B virus (HBV), may play a role in the formation of, and/or the selection for, this mutation The primary DNA adduct of AFB1 is 8,9-dihydro-8-(N7-guanyl)-9-hydroxyaflatoxin B1 (AFB1-N7-Gua), which is converted naturally to two secondary lesions, an apurinic site and an AFB1-formamidopyrimidine (AFB1-FAPY) adduct AFB1-FAPY is detected at near maximal levels in rat DNA days to weeks after AFB1 exposure, underscoring its high persistence in vivo The present study reveals two striking properties of this DNA adduct: (i) AFB1-FAPY was found to cause a G to T mutation frequency in Escherichia coli approximately 6 times higher than that of AFB1-N7-Gua, and (ii) one proposed rotamer of AFB1-FAPY is a block to replication, even when the efficient bypass polymerase MucAB is used by the cell Taken together, these characteristics make the FAPY adduct the prime candidate for both the genotoxicity of aflatoxin, because mammalian cells also have similar bypass mechanisms for combating DNA damage, and the mutagenicity that ultimately may lead to liver cancer

https://www.pnas.org/content/pnas/99/10/6655.full.pdf

The aflatoxin B1 formamidopyrimidine adduct plays a major role in causing the types of mutations observed in human hepatocellular carcinoma

Acrolein and higher alpha,beta-unsaturated aldehydes are bifunctional genotoxins The deoxyguanosine adduct of acrolein, 3-(2-deoxy-beta-d-erythro-pentofuranosyl)-5,6,7,8-tetrahydro-8-hydroxypyrimido[1,2-a]purin-10(3H)-one (8-hydroxy-1,N(2)-propanodeoxyguanosine, 2a), is a major DNA adduct formed by acrolein The potential for oligodeoxynucleotide duplexes containing 2a to form interchain cross-links was evaluated by HPLC, CZE, MALDI-TOF, and melting phenomena Interchain cross-links represent one of the most serious types of damage in DNA since they are absolute blocks to replication In oligodeoxynucleotides containing the sequence 5'-dC-2a, cross-linking occurred in a slow, reversible manner to the extent of approximately 50% Enzymatic digestion to form 3-(2-deoxy-beta-d-erythro-pentofuranosyl)-5,6,7,8-tetrahydro-8-(N(2)-2'-deoxyguanosinyl)pyrimido[1,2-a]purin-10(3H)one (5a) and reduction with NaCNBH(3) followed by enzymatic digestion to give 1,3-bis(2'-deoxyguanosin-N(2)-yl)propane (6a) established that cross-linking had occurred with the exocyclic amino group of deoxyguanosine It is concluded that the cross-link is a mixture of imine and carbinolamine structures With oligodeoxynucleotide duplexes containing the sequence 5'-2a-dC, cross-links were not detected by the techniques enumerated above In addition, (15)N-(1)H HSQC and HSQC-filtered NOESY spectra carried out with a duplex having (15)N-labeling of the target amino group established unambiguously that a carbinolamine cross-link was not formed The potential for interchain cross-link formation by the analogous crotonaldehyde adduct (2b) was evaluated in a 5'-dC-2b sequence Cross-link formation was strongly dependent on the configuration of the methyl group at C6 of 2b The 6R diastereomer of 2b formed a cross-link to the extent of 38%, whereas the 6S diastereomer cross-linked only 5%

Constance M. Harris

Papers

Vancomycin: structure and transformation to CDP-I

The aflatoxin B1 formamidopyrimidine adduct plays a major role in causing the types of mutations observed in human hepatocellular carcinoma

DNA interchain cross-links formed by acrolein and crotonaldehyde.

The role of the chlorine substituents in the antibiotic vancomycin: preparation and characterization of mono- and didechlorovancomycin

Synthesis of polyketide-type aromatic natural products by biogenetically modeled routes