多肽聚合物合成新方法及生物医学应用

多肽聚合物是以多肽为主链的合成聚合物,由于其固有的生物相容性和生物降解性,在生物医学领域展现出广阔的应用前景,然而多肽聚合物的高效、快速、简便合成仍然具有很大挑战。近年来随着合成化学的快速发展,基于α-氨基酸的N-羧基环内酸酐(NCA)开环聚合法制备多肽聚合物取得了突破性进展,合成了大量基于多肽聚合物的新型材料。本文首先介绍了NCA单体的合成机理及最新改进,然后重点介绍了近年来新发展的NCA开环聚合快速、高效制备多肽聚合物的不同引发或催化体系,最后简要介绍了多肽聚合物在抗菌剂、药物递送及组织工程等领域的应用,并提出了多肽聚合物材料在生物医学领域应用所面临的挑战。     

ML／Y分子筛复合材料的制备,表征及其催化性能研究

采用沸石合成法制备了ＭＬ／Ｙ（Ｍ＝ Ｆｅ,Ｃｏ,Ｃｒ;Ｌ＝ ８－ ｑｕｉｎｏｌｉｎｏｌａｎｄ ｓａｌｉｃｙｌｉｃ ａｃｉｄ （ｄｅｎｏｔｅｄ ａｓＱｘ ａｎｄ ＳＡｒｅｓｐｅｃｔｉｖｅｌｙ）） 复合材料,并通过ＸＲＤ、ＦＴＩＲ、ＩＣＰ、ＵＶ－ ｖｉｓ 及催化反应等手段对其进行了表征。ＦＴＩＲ和ＵＶ－ ｖｉｓ 测试结果表明： 合成体系中含有的金属配合物经过水热晶化后封装或固定在分子筛的空腔中。通过Ｘ射线衍射原位跟踪Ｙ型分子筛的晶化过程,发现合成体系中含有金属配合物的性质及其量的多少不仅对Ｙ型分子筛的晶化有很大影响,而且使其封装或固定在分子筛中的量也有所差异。另外,以环己烷氧化为探针反应考察了ＭＬ／Ｙ的催化性能,结果表明ＭＬ／Ｙ的氧化能力来自于所封装或固定的金属配合物,其氧化能力主要取决于配合物中心离子的性质     

Apoptolidin: induction of apoptosis by a natural product

Apoptolidin is a natural product that selectively induces apoptosis in several cancer cell lines. Apoptosis, programmed cell death, is a biological key pathway for regulating homeostasis and morphogenesis. Apoptotic misregulations are connected with several diseases, in particular cancer. The extrinsic way to apoptosis leads through death ligands and death receptors to the activiation of the caspase cascade, which results in proteolytic degradation of the cell architecture. The intrinsic pathway transmits signals of internal cellular damage to the mitochondrion, which loses its structural integrity, and forms an apoptosome that initiates the caspase cascade. Compounds which regulate apoptosis are of high medical significance. Many natural products regulate apoptotic pathways, and apoptolidin is one of them. The known synthetic routes to apoptolidin are described and compared in this Review. Selected further natural products which regulate apoptosis are introduced briefly.     

手性药物的酶催化不对称定向合成

手性药物目前已成为国际上新药研究的热点。手性药物及其中间体的酶催化定向合成与传统的有机合成反应相比,所需条件温和,无需强酸强碱、高温高压等极端条件,可大大降低对设备的要求,同时具备反应速度快、立体选择性高等优势,而且对环境污染小,属于绿色合成技术,因而成为制备手性化合物的最有前景的方法之一。本文主要介绍了手性药物的酶催化不对称定向合成的方式、催化机理及应用,并引入了一些最新进展情况。     

Mesoporous materials for drug delivery

Research on mesoporous materials for biomedical purposes has experienced an outstanding increase during recent years. Since 2001, when MCM-41 was first proposed as drug-delivery system, silica-based materials, such as SBA-15 or MCM-48, and some metal-organic frameworks have been discussed as drug carriers and controlled-release systems. Mesoporous materials are intended for both systemic-delivery systems and implantable local-delivery devices. The latter application provides very promising possibilities in the field of bone-tissue repair because of the excellent behavior of these materials as bioceramics. This Minireview deals with the advances in this field by the control of the textural parameters, surface functionalization, and the synthesis of sophisticated stimuli-response systems.     

Computational Drug Repurposing Based on a Recommendation System and Drug–Drug Functional Pathway Similarity

Drug repurposing identifies new clinical indications for existing drugs. It can be used to overcome common problems associated with cancers, such as heterogeneity and resistance to established therapies, by rapidly adapting known drugs for new treatment. In this study, we utilized a recommendation system learning model to prioritize candidate cancer drugs. We designed a drug–drug pathway functional similarity by integrating multiple genetic and epigenetic alterations such as gene expression, copy number variation (CNV), and DNA methylation. When compared with other similarities, such as SMILES chemical structures and drug targets based on the protein–protein interaction network, our approach provided better interpretable models capturing drug response mechanisms. Furthermore, our approach can achieve comparable accuracy when evaluated with other learning models based on large public datasets (CCLE and GDSC). A case study about the Erlotinib and OSI-906 (Linsitinib) indicated that they have a synergistic effect to reduce the growth rate of tumors, which is an alternative targeted therapy option for patients. Taken together, our computational method characterized drug response from the viewpoint of a multi-omics pathway and systematically predicted candidate cancer drugs with similar therapeutic effects.     

Micro- and Nanocapsules Based on Artificial Peptides

The encapsulation of active ingredients into solid capsules from biodegradable materials has received significant attention over the last decades. In this short review, we focus on the formation of micro- and nano-sized capsules and emulsions based on artificial peptides as a fully degradable material. It deals with various approaches for the preparation of peptide-based capsules as well as with their crucial properties such as size and stability. We categorize all preparation procedures into three basic approaches: self-assembly, polymerization and crosslinking, and layer-by-layer technology. This article is meant to offer a short overview over all successful methods suitable for obtaining access to these very promising carrier systems.     

溶胶-凝胶法制备纳米SiO2包覆的铝颜料

铝颜料是重要的金属颜料之一,当其用于水性涂料时,易被腐蚀而逐渐失去金属光泽,为了提高铝颜料的耐碱性,在乙醇/水体系中,采用溶胶-凝胶法制备了纳米SiO2包覆的铝颜料,利用SEM、XRD和FTIR分析手段对其进行了表征,并考察了其耐碱性.结果表明:当体系原料H2O/NH3/TEOS的摩尔比为32.7∶4.4∶1时,SiO2可以在铝颜料表面形成致密的保护膜;铝颜料经SiO2包覆处理后,其耐碱性大大提高,在pH=11的溶液中放置60天后,没有任何H2产生,表明经SiO2包覆处理的铝颜料具有优异的耐碱性.     

Optimization of Biocompatibility for a Hydrophilic Biological Molecule Encapsulation System

Despite considerable advances in recent years, challenges in delivery and storage of biological drugs persist and may delay or prohibit their clinical application. Though nanoparticle-based approaches for small molecule drug encapsulation are mature, encapsulation of proteins remains problematic due to destabilization of the protein. Reverse micelles composed of decylmonoacyl glycerol (10MAG) and lauryldimethylamino-N-oxide (LDAO) in low-viscosity alkanes have been shown to preserve the structure and stability of a wide range of biological macromolecules. Here, we present a first step on developing this system as a future platform for storage and delivery of biological drugs by replacing the non-biocompatible alkane solvent with solvents currently used in small molecule delivery systems. Using a novel screening approach, we performed a comprehensive evaluation of the 10MAG/LDAO system using two preparation methods across seven biocompatible solvents with analysis of toxicity and encapsulation efficiency for each solvent. By using an inexpensive hydrophilic small molecule to test a wide range of conditions, we identify optimal solvent properties for further development. We validate the predictions from this screen with preliminary protein encapsulation tests. The insight provided lays the foundation for further development of this system toward long-term room-temperature storage of biologics or toward water-in-oil-in-water biologic delivery systems.     

Rational Design and Synthesis of HSF1-PROTACs for Anticancer Drug Development

PROTACs employ the proteosome-mediated proteolysis via E3 ligase and recruit the natural protein degradation machinery to selectively degrade the cancerous proteins. Herein, we have designed and synthesized heterobifunctional small molecules that consist of different linkers tethering KRIBB11, a HSF1 inhibitor, with pomalidomide, a commonly used E3 ligase ligand for anticancer drug development.