Otvos Laszlo
Sbarro Institute for Cancer Research and Molecular Medicine, Temple University, Philadelphia, PA, USA.
Methods Mol Biol. 2008;494:1-8. doi: 10.1007/978-1-59745-419-3_1.
After many years of stagnation, peptide therapeutics once again became the focus of innovative drug development efforts backed up by venture funds and biotechnology companies. Designer peptide drugs overcome the unattractive pharmacological properties of native peptides and protein fragments and frequently feature nonnatural amino acid or backbone replacements, cyclic or multimeric structures, or peptidic or nonpeptidic delivery modules. With their high specificity and low toxicity profile, biologicals offer viable alternatives to small molecule therapeutics. The development of peptide drugs requires specific considerations of this family of biopolymers. Historically, peptide vaccines to viral infections and antibacterial peptides led the way in clinical development, but recently many other diseases have been targeted, including the big sellers AIDS, cancer, and Alzheimer's disease. This book gives practical advice to the most important steps in peptide-based drug development such as isolation, purification, characterization, interaction with targets, structural analysis, stability studies, assessment of biodistribution and pharmacological parameters, sequence modifications, and high throughput screening. This brief overview provides historical background for each of the listed techniques and diseases.
经过多年的停滞不前，肽类疗法再度成为创新药物研发努力的焦点，得到了风险投资基金和生物技术公司的支持。设计型肽类药物克服了天然肽和蛋白质片段缺乏吸引力的药理学特性，并且常常具有非天然氨基酸或主链替换、环状或多聚体结构，或者肽类或非肽类递送模块。凭借其高特异性和低毒性特征，生物制品为小分子疗法提供了可行的替代方案。肽类药物的研发需要对这一类生物聚合物进行特殊考量。从历史上看，针对病毒感染的肽类疫苗和抗菌肽引领了临床开发的道路，但最近许多其他疾病也成为了目标，包括畅销的艾滋病、癌症和阿尔茨海默病。本书针对基于肽的药物开发中的最重要步骤提供了实用建议，例如分离、纯化、表征、与靶点的相互作用、结构分析、稳定性研究、生物分布和药理学参数评估、序列修饰以及高通量筛选。这一简要概述为所列的各项技术和疾病提供了历史背景。
