다중혈관 관상동맥 환자에서 y-문합을 이용하여 양쪽 내흉동맥만을 사용한 우회술의 조기 성적

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

Examination of nature's favorite molecules reveals a striking preference for making carbon-heteroatom bonds over carbon-carbon bonds-surely no surprise given that carbon dioxide is nature's starting material and that most reactions are performed in water. Nucleic acids, proteins, and polysaccharides are condensation polymers of small subunits stitched together by carbon-heteroatom bonds. Even the 35 or so building blocks from which these crucial molecules are made each contain, at most, six contiguous C-C bonds, except for the three aromatic amino acids. Taking our cue from nature's approach, we address here the development of a set of powerful, highly reliable, and selective reactions for the rapid synthesis of useful new compounds and combinatorial libraries through heteroatom links (C-X-C), an approach we call "click chemistry". Click chemistry is at once defined, enabled, and constrained by a handful of nearly perfect "spring-loaded" reactions. The stringent criteria for a process to earn click chemistry status are described along with examples of the molecular frameworks that are easily made using this spartan, but powerful, synthetic strategy.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1002/1521-3773%2820010601%2940%3A11%3C2004%3A%3AAID-ANIE2004%3E3.0.CO%3B2-5

Click Chemistry: Diverse Chemical Function from a Few Good Reactions.

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

Marine natural products.

CA : A Cancer Journal for Clinicians

Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA

Fanconi Anemia (FA) patients are at risk for head and neck squamous cell carcinomas. Their normal tissue radiosensitivity often presents a challenge to deliver radiotherapy. Locally applied GS-nitroxide JP4-039 radioprotects the oral mucosa of Fancd2-/-(129/Sv) mice from single fraction or fractionated irradiation (Berhane et al, Radiation Research 182:35-49, 2014). We sought to prove that JP4-039 targets the mitochondria of the oral mucosal cells, and protects normal tissue in vivo, but does not prevent radiocontrolability of tumors. Fancd2+/+, Fancd2+/- and Fancd2-/- mice of a different background strain (C57BL/6), received intraoral flurochrome labelled bodipy-JP4-039 in F15 liposomes, were sacrificed 2 hr later and the oral mucosa removed sectioned, and stained with an antibody to mitochondrial protein TOM-20 and examined microscopically for co-localization of bodipy-JP4-039. Mitochondria were isolated from explanted oral mucosal cells and uptake of JP4-039 compared to non-mitochondrial targeted Tempo, measured using EPR. Fancd2+/+, Fancd2+/- and Fancd2-/- mice with orthotopic TC-1 murine squamous cell tumors were treated with JP-4-039/F15, then irradiated. Mitochondrial uptake in normal tissue but not tumors was demonstrated by co-localization of Bodipy-JP4-039 and mitochondrial protein TOM-20. EPR analysis of purified mitochondria from explanted oral cavity cells of Fancd2+/+ and Fancd2-/- mice treated with F15-JP4-039 showed a 15.6 and 19.1 fold increased uptake of nitroxide signal in JP4-039 treated mice, respectively, compared to Tempo uptake in mitochondria . There was no significant difference in tumor control between the JP4-039/F15 treated then irradiated compared to control irradiated mice, in any of the 3 genotypes: Fancd2+/+ group, p = 0.6851; Fancd2+/− group p = 0.7174 and p = 0.7559 in the Fancd2−/− group. JP4-039/F15 administration prior to either single fraction 28 Gy or prior to each fraction of fractionated head and neck irradiation (8 Gy x 4) showed significant normal tissue protection (decreased ulceration) but not tumor radioprotection. Irradiation reduced tumor volume in mice of all genotypes with no detectable effect of JP4-039/F15. Specifically, with wild type Fancd2+/+ mice after 28 Gy, there was no radioprotective effect of JP4-039/F15 on tumor regrowth (p = 0.7520). Tumor bearing Fancd2−/− (p = 0.1843) and Fancd2+/− mice also showed normal tissue but not tumor protection (p = 0.4106 and p = 0.1843, respectively). The data support use of normal mucosal radioprotective JP4-039/F15 during radiotherapy of FA patients with head and neck cancer.

Citation Format: Michael W. Epperly, Ashwin Shinde, Hebist Berhane, Byung Han Rhieu, Ronny Kalash, Karen Xu, Darcy Franicola, Xichen Zhang, Tracy Dixon, Donna Shields, Hong Wang, Peter Wipf, Kalindi Parmar, Eva Guinan, Valerian Kagan, Yulia Tyurina, Robert L. Ferris, Song Li, Joel S. Greenberger. Intraoral administration of mitochondrial targeted GS-nitroxide (JP4-039) radioprotects the oral mucosa but not orthotopic tumors in Fancd2-/- mice. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3340. doi:10.1158/1538-7445.AM2015-3340

Abstract 3340: Intraoral administration of mitochondrial targeted GS-nitroxide (JP4-039) radioprotects the oral mucosa but not orthotopic tumors in Fancd2-/- mice

Microwave‐Assisted “Libraries from Libraries” Approach Toward the Synthesis of Allyl‐ and C‐Cyclopropylalkylamides.

A readily recyclable, fluorous alkoxy ethyl ether protecting group has been developed that allows for simple purification of small to medium-sized organic molecules by liquid-liquid extraction with FC-72/organic/aqueous solvents. The precursor vinyl ether 3 can be prepared in large quantity in a straightforward two step reaction sequence. Primary, secondary, and tertiary alcohols are protected in good to excellent yields, and the fluorous label is removed by mild acid treatment. The N -protection of 2-fluoroaniline demonstrates the feasibility of using 3 with amines.

Peter Wipf

Papers

Abstract 3340: Intraoral administration of mitochondrial targeted GS-nitroxide (JP4-039) radioprotects the oral mucosa but not orthotopic tumors in Fancd2-/- mice

Microwave‐Assisted “Libraries from Libraries” Approach Toward the Synthesis of Allyl‐ and C‐Cyclopropylalkylamides.

Synthesis and Applications of a Highly Fluorous Alkoxy Ethyl Ether Protective Group.

Total Synthesis of the Spiroketal Naphthoquinone (.+-.)-Diepoxin σ.

Cell-active dual specificity phosphatase inhibitors identified by high-content screening.