Theonellamides J and K and 5-cis-Apoa-theopalauamide,Bicyclic Glycopeptides of the Red Sea Sponge Theonella swinhoei

Theonella swinhoei is a fairly common inhabitant of reefs throughout the Indian and Pacific Oceans. Metabolomic analyses of samples of T. swinhoei collected in different depths in the Gulf of Aqaba revealed two chemotypes differing in the profiles of the theonellamides they produce, some of which seem to be unknown. Driven by this finding, we examined a sample of T. swinhoei collected more than 40 years ago in the southern part of the Gulf of Aqaba. Large-scale extract of this sample yielded four theonellamides, the known theopalauamide (4), as the major component, and three new metabolites, theonellamide J (1), 5-cis-Apoa-theopalauamide (2), and theonellamide K (3), as the minor components. The planar structure of these complex cyclic glycopeptides was elucidated by combination of 1D and 2D NMR techniques and HRESIMS. The absolute configuration of the amino acids was established by Marfey’s and advanced Marfey’s methods, and the absolute configuration of its galactose unit using “Tanaka’s method” for monosaccharides. The biological activity of the pure compounds was tested for antibacterial activity and for cytotoxicity to HTC-116 cell line. The compounds presented significant cytotoxicity against the HTC-116 cell line, illuminating the importance of the Apoa subunit for the activity.     

高效凝胶渗透色谱法测定人参糖肽注射液的重均分子量

建立人参糖肽注射液分子量分布测定方法。色谱柱为多糖专用凝胶柱OHpak SB-802HQ（8mm×300mm）,以0．9％氯化钠为流动相,流速0.5mL／min,示差折光检测器。人参糖肽注射液重均分子量为900—1100u。本实验建立的多糖分子量测定方法具有简便、快速和重现性好的特点,为提高和完善该制剂的质量标准提供了依据,同时可作为指纹图谱从多糖肽分子量角度来控制该产品的内在质量。     

大鲵糖肽组分的高效液相色谱分析及其抗氧化活性研究

利用高效液相色谱方法对大鲵糖肽进行分析,使用Sino Chrom C18反相柱和紫外可变波长检测器,并测定大鲵糖肽的羟基自由基清除能力。结果表明：大鲵糖肽组分的最佳液相色谱检测条件为：检测波长280 nm;流动相为V（乙腈）∶V（甲醇）∶V（0.1%三氟乙酸）=5∶5∶90;流速1.0 mL/min;进样量20μL。大鲵糖肽在5.78μg/mL浓度时,羟基自由基的清除率达60.19%,具有较好的抗氧化活性。     

Antifreeze Peptides and Glycopeptides,and Their Derivatives: Potential Uses in Biotechnology

Antifreeze proteins (AFPs) and glycoproteins (AFGPs), collectively called AF(G)Ps, constitute a diverse class of proteins found in various Arctic and Antarctic fish, as well as in amphibians, plants, and insects. These compounds possess the ability to inhibit the formation of ice and are therefore essential to the survival of many marine teleost fishes that routinely encounter sub-zero temperatures. Owing to this property, AF(G)Ps have potential applications in many areas such as storage of cells or tissues at low temperature, ice slurries for refrigeration systems, and food storage. In contrast to AFGPs, which are composed of repeated tripeptide units (Ala-Ala-Thr)_n with minor sequence variations, AFPs possess very different primary, secondary, and tertiary structures. The isolation and purification of AFGPs is laborious, costly, and often results in mixtures, making characterization difficult. Recent structural investigations into the mechanism by which linear and cyclic AFGPs inhibit ice crystallization have led to significant progress toward the synthesis and assessment of several synthetic mimics of AFGPs. This review article will summarize synthetic AFGP mimics as well as current challenges in designing compounds capable of mimicking AFGPs. It will also cover our recent efforts in exploring whether peptoid mimics can serve as structural and functional mimics of native AFGPs.     

Glycosylation of Conotoxins

Conotoxins are small peptides present in the venom of cone snails. The snail uses this venom to paralyze and capture prey. The constituent conopeptides display a high level of chemical diversity and are of particular interest for scientists as tools employed in neurological studies and for drug development, because they target with exquisite specificity membrane receptors, transporters, and various ion channels in the nervous system. However, these peptides are known to contain a high frequency and variability of post-translational modifications—including sometimes O-glycosylation—which are of importance for biological activity. The potential application of specific conotoxins as neuropharmalogical agents and chemical probes requires a full characterization of the relevant peptides, including the structure of the carbohydrate part. In this review, the currently existing knowledge of O-glycosylation of conotoxins is described.     

Renal corpuscle development in boreal fishes with and without antifreezes

Light and election microscopy were used to document the degree of renal corpuscle development in boreal telcost fishes that produce peptide or glycopeptide antifreeze compounds on a seasonal or permanent basis. Emphasis was placed on gadids, cottids and pleuronectids from both the North Atlantic and North Pacific Oceans. Based on the classification of Marshall and Smith (1930), corpuscle development ranged from fully glomerular (Type 1) to pauciglomerular (Type III). Unlike the situation in Antarctic notothenioid fishes, there were no aglomerular species among the boreal fishes. Corpuscles were small in diameter in gadids whereas in cottids they ranged from small to large with considerable intraspecific variation. Eight of eleven species with antifreeze had intermediate (Type II–III) or pauciglomerular kidneys with relatively few dense corpuscles (dia. 36–82m). In some of these species an extensive mesangium and a substantial capillary endothelium contributed to a glomerular filtration barrier that was four to five times thicker than that in Type I kidneys. The corpuscles of other pauciglomerular species were unremarkable and appeared functional at the ultrastructural level. The boreal fish fauna is taxonomically diverse and, compared to the unrelated Antarctic fauna, of relatively recent evolutionary origin. Furthermore, antifreeze is present only during the winter in some species. Hence it is not surprising that the urinary conservation of antifreeze is accomplished by mechanisms other than the evolutionary loss of renal corpuscles.     

Theonellamide G,a Potent Antifungal and Cytotoxic Bicyclic Glycopeptide from the Red Sea Marine Sponge Theonella swinhoei

In our search for bioactive metabolites from marine organisms, we have investigated the polar fraction of the organic extract of the Red Sea sponge Theonella swinhoei. Successive chromatographic separations and final HPLC purification of the potent antifungal fraction afforded a new bicyclic glycopeptide, theonellamide G (1). The structure of the peptide was determined using extensive 1D and 2D NMR and high-resolution mass spectral determinations. The absolute configuration of theonellamide G was determined by chemical degradation and 2D NMR spectroscopy. Theonellamide G showed potent antifungal activity towards wild and amphotericin B-resistant strains of Candida albicans with IC₅₀ of 4.49 and 2.0 μM, respectively. Additionally, it displayed cytotoxic activity against the human colon adenocarcinoma cell line (HCT-16) with IC₅₀ of 6.0 μM. These findings provide further insight into the chemical diversity and biological activities of this class of compounds.     

糖肽类抗生素的研究进展

糖肽类抗生素,尤其是万古霉素是临床治疗耐甲氧西林金黄色葡萄球菌(methicillin-resistant Staphylococcus aureus,MRSA)等多重耐药的革兰阳性菌感染的有效药物。由于糖肽类抗生素耐药性问题愈加严重,寻找和开发新的化合物应用于临床治疗变得十分紧迫。本文就糖肽类抗生素的作用与耐药机制、新批准的糖肽类抗菌药物、化学修饰与新的筛选开发手段展开综述,以期对糖肽类抗生素药物的开发提供思路。