Molecular Recognition in Dendrimers Based on Melamine

基于三聚氰胺的树枝状聚合物的分子识别

• 批准号: 7475688
• 负责人: ERIC E SIMANEK
• 金额: $ 24.52万
• 依托单位: TEXAS A&M UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7475688
• 关键词: Acute; Antibodies; Architecture; Area; B-Lymphocytes; Biocompatible; Biodistribution; Biological Assay; Biological Availability; Bioluminescence; Breast; Chemicals; Chronic; Class; Classification; Clinical Trials; Complex; Crowding; Cytotoxic agent; Dendrimers; Development; Diagnostic Imaging; Diamines; Disease regression; Drug Delivery Systems; Elements; Excretory function; Feedback; Generations; Goals; Immune system; Immunoglobulin Constant Region; Isotopes; Link; Localized; Malignant neoplasm of prostate; Measures; Melamine; Metabolism; Micelles; Molecular; Molecular Conformation; Numbers; Organic Chemistry; Pharmaceutical Preparations; Phase; Polymers; Positron-Emission Tomography; Preparation; Property; Prostate; Prostate Cancer Vaccine; Prostatic Neoplasms; Proteins; Radio; Rate; Research; Research Personnel; Role; Route; Shapes; Solid Neoplasm; Structure; Synthetic Vaccines; System; T-Lymphocyte; Therapeutic; Time; Toxic effect; Transfection; Treatment Efficacy; Triazines; Vaccines; Variant; Water; absorption; antibody conjugate; base; concept; design; macromolecule; molecular recognition; nanoscale; next generation; programs; size; success; tumor

DESCRIPTION (provided by applicant): Dendrimers are an understudied class of nanometer-scale, globular polymers that offer candidates for the next-generation of polymer therapeutics. Size, shape, and composition impact all aspects of these vehicles including overall efficacy, bioavailability, toxicity, metabolism, absorption and excretion. Optimization of these parameters for drug delivery using dendrimers requires (1) exquisite control over the synthesis of dendrimer candidates; (2) an understanding of the physical organic chemistry of these macromolecules and macromolecule-drug complexes; and finally, (3) assessment of therapeutic efficacy. To date, owing to synthetic routes that lack an approach for systematic variation of size, shape, and composition as well as number of architectures for structure-property relationships (the hallmark of physical organic chemistry), there is little fundamental understanding of the design criteria for the use of dendrimers in drug delivery. There are three overall aims of proposed research which focuses on breast and prostate tumors: Specific Aim #1: Examine the fundamental physical organic chemistry of these macromolecules as it pertains to: 1 A) The number of "phases" a biocompatible PEGylated dendrimer comprises in water and the impact that this has on the sequestration of drugs: In monophasic dendrimers, sequestration is proportional to MW. 1B) The ability to tailor release rates of drugs through systematic cleavage of bioloabile linkers in architectures showing a gradient of tethers and steric crowding. 1C) The global conformation of these macromolecules and the guests associated with them. Specific Aim #2: Identify the molecular determinants for biodistribution and tumor targeting using multifuctional dendrimers. Specific Aim #3: Explore macromolecular recognition to determine the molecular parameters that allow these dendrimers to serve as synthetic vaccines and as multi-functional adaptor units on antibodies.

描述（由申请人提供）：树枝状聚合物是一类研究的纳米尺度，球状聚合物，为下一代聚合物治疗剂提供候选者。大小，形状和组成影响这些车辆的所有方面，包括总体功效，生物利用度，毒性，代谢，吸收和排泄。使用树枝状聚合物优化这些参数以递送药物，需要（1）对树枝状聚合物候选物的合成的精美控制； （2）对这些大分子和大分子毒物配合物的物理有机化学的理解；最后，（3）评估治疗功效。迄今为止，由于缺乏系统变化的综合途径，大小，形状和组成以及结构 - 质体关系的架构数量（物理有机化学的标志），几乎没有对在药物输送中使用树枝状聚合物使用的设计标准的基本了解。拟议研究的总体目的是三个总体，重点是乳腺癌和前列腺肿瘤： 具体目的＃1：检查这些大分子的基本物理有机化学与：1 a）“相”的“相”数量的生物相容性的聚乙二醇化树状聚合物在水中以及对药物的序列包含的影响：在单相结构物中具有序列的序列，序列序列是序列，序列是序列化的。 1B）通过在体系结构中系统切割的造物裂解，能够量身定制药物的释放速率，以显示割草机和空间拥挤的梯度。 1C）这些大分子和与之相关的客人的全球构型。 特定目标＃2：确定使用多因素树状聚合物靶向生物分布和肿瘤的分子决定因素。 特定目标＃3：探索大分子识别，以确定允许这些树枝状聚合物作为合成疫苗的分子参数，并用作抗体上的多功能适配器单元。