Development of a peptide array synthesis system

描述（由申请人提供）：本提案的I期和II期的总体目标是开发用于蛋白质高通量分析的基于微阵列的方法。这将以两种不同的方式完成，一种是基于1平方厘米芯片上的数十万种不同肽的阵列，可用于对蛋白质进行指纹识别，另一种是基于数千或数万种针对蛋白质的抗体，仅给出蛋白质的基因组序列。这两种方法都需要一个制造商来廉价和快速地生产高密度肽阵列。特别是，第一阶段的目标如下：1.合成光不稳定氨基酸2.将光不稳定氨基酸附着到氨基载玻片上。3.确定最佳脱保护时间和适当的溶剂条件。提高氨基酸偶联每步的产率。4.合成肽阵列。5.小规模演示已知肽蛋白相互作用的系统，建立信号再现性和响应特性。6.开发计算机模拟方法，以有效地选择数百万种不同的肽序列，从而使数十种不同的序列几乎可以结合阵列上呈现的任何蛋白质。

DESCRIPTION (provided by applicant): The overall goal of phase I and II of this proposal is to develop microarray-based methods for high throughput profiling of proteins. This will be done in two different ways, one based on arrays of 100s of thousands of distinct peptides on 1 cm2 chips that can be used to fingerprint proteins, the other based on thousands or tens of thousands of antibodies against proteins, given only the genomic sequence of the proteins. Both methods require a fabricator for producing high density peptide arrays inexpensively and rapidly. In particular, phase I has the following aims: 1. Synthesize photolabile- amino acids 2. Attach photolabile amino acids to amino-glass slide. 3. Determine optimum deprotection time and appropriate solvent conditions. Improve the yield per step of amino acid coupling. 4. Synthesize peptide arrays. 5. Demonstrate the systems on a small scale for known peptide protein interactions, establishing signal reproducibility and response characteristics. 6. Develop in silico methods to effectively select millions of different peptide sequences such that tens of different sequences will bind virtually any protein presented to the array.