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

Automated structure validation was introduced in chemical crystallography about 12 years ago as a tool to assist practitioners with the exponential growth in crystal structure analyses. Validation has since evolved into an easy-to-use checkCIF/PLATON web-based IUCr service. The result of a crystal structure determination has to be supplied as a CIF-formatted computer-readable file. The checking software tests the data in the CIF for completeness, quality and consistency. In addition, the reported structure is checked for incomplete analysis, errors in the analysis and relevant issues to be verified. A validation report is generated in the form of a list of ALERTS on the issues to be corrected, checked or commented on. Structure validation has largely eliminated obvious problems with structure reports published in IUCr journals, such as refinement in a space group of too low symmetry. This paper reports on the current status of structure validation and possible future extensions.

/pdf/structure-validation-in-chemical-crystallography-487m3el0s4.pdf

Structure validation in chemical crystallography

The results of a single-crystal structure determination when in CIF format can now be validated routinely by automatic procedures. In this way, many errors in published papers can be avoided. The validation software generates a set of ALERTS detailing issues to be addressed by the experimenter, author, referee and publication journal. Validation was pioneered by the IUCr journal Acta Crystallographica Section C and is currently standard procedure for structures submitted for publication in all IUCr journals. The implementation of validation procedures by other journals is in progress. This paper describes the concepts of validation and the classes of checks that are carried out by the program PLATON as part of the IUCr checkCIF facility. PLATON validation can be run at any stage of the structure refinement, independent of the structure determination package used, and is recommended for use as a routine tool during or at least at the completion of every structure determination. Two examples are discussed where proper validation procedures could have avoided the publication of incorrect structures that had serious consequences for the chemistry involved.

/pdf/single-crystal-structure-validation-with-the-program-platon-2pdiuo25f2.pdf

Single-crystal structure validation with the program PLATON

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

Marine natural products.

Shared principles in NF-kappaB signaling

We describe the synthesis and properties of a small molecule mimic of Smac, a pro-apoptotic protein that functions by relieving inhibitor-of-apoptosis protein (IAP)-mediated suppression of caspase activity The compound binds to X chromosome- encoded IAP (XIAP), cellular IAP 1 (cIAP-1), and cellular IAP 2 (cIAP-2) and synergizes with both tumor necrosis factor alpha (TNFalpha) and TNF-related apoptosis-inducing ligand (TRAIL) to potently induce caspase activation and apoptosis in human cancer cells The molecule has allowed a temporal, unbiased evaluation of the roles that IAP proteins play during signaling from TRAIL and TNF receptors The compound is also a lead structure for the development of IAP antagonists potentially useful as therapy for cancer and inflammatory diseases

https://science.sciencemag.org/content/sci/305/5689/1471.full.pdf

A Small Molecule Smac Mimic Potentiates TRAIL- and TNFα-Mediated Cell Death

Autocrine TNFα Signaling Renders Human Cancer Cells Susceptible to Smac-Mimetic-Induced Apoptosis

A concise and flexible total synthesis of (-)-diazonamide A.

In the preceding communication we described a fully synthetic pathway to the structure proposed for ( )-diazonamide A (1, Scheme 1).[1] This material is not identical to the natural product, which raises the obvious question: What is the true structure of diazonamide A? Herein we provide an answer. In addition, we report that defined synthetic entity 8 induces, with equal potency, a toxic phenotype in cell culture indistinguishable from that produced by natural ( )-diazonamide A. Spectroscopic data for the heterocyclic cores of diazonamides A and B are nearly identical.[2] So when the crystal structure of a p-bromobenzamide derivative of diazonamide B was reported as 3,[2a] the diazonamide A assignment Scheme 1. Initial diazonamide structure assignments.

/pdf/total-synthesis-of-nominal-diazonamides-part-2-on-the-true-1wbo1yfqqi.pdf

Total Synthesis of Nominal Diazonamides—Part 2: On the True Structure and Origin of Natural Isolates

Representative procedure for the preparation of 7: A solution of lithium hexamethyldisilazide in THF (1, 0.20 mL, 0.20 mmol) was added dropwise to a solution of 1 (0.038 g; 0.20 mmol) in THF (0.5 mL) at 78C. The resulting pale yellow solution was stirred for 10 min at the same temperature, and then a solution of coumarin 2b (0.032 g; 0.22 mmol) in THF (0.5 mL) was added dropwise at 78C. After 30 min, a solution of trans chalcone 5c (0.045 g, 0.22 mmol) was added dropwise. The reaction mixture was stirred for a further 30 min at the same temperature, and then a solution of trimethylsilyl chloride (0.31 mL) in methanol (5 mL) was added at 78C. The reaction mixture was warmed to room temperature overnight. The solvents were removed in vacuo to give the crude product, which was purified by column chromatography (1:1 petroleum ether/ethyl

Patrick G. Harran

Papers

A Small Molecule Smac Mimic Potentiates TRAIL- and TNFα-Mediated Cell Death

Autocrine TNFα Signaling Renders Human Cancer Cells Susceptible to Smac-Mimetic-Induced Apoptosis

A concise and flexible total synthesis of (-)-diazonamide A.

Total Synthesis of Nominal Diazonamides—Part 2: On the True Structure and Origin of Natural Isolates

Total Synthesis of Nominal Diazonamides—Part 1: Convergent Preparation of the Structure Proposed for (−)-Diazonamide A