Nikolaiev V, Stierandová A, Krchnák V, Seligmann B, Lam K S, Salmon S E, Lebl M
Selectide Corporation, Tucson, AZ 85737.
Pept Res. 1993 May-Jun;6(3):161-70.
A method of indirectly determining the structure of nonpeptidic or nonsequenceable compounds that have been synthesized on individual particles of solid support is described. The technique permits the parallel synthesis of a compound that is not susceptible to Edman degradation (e.g., N-terminal-blocked peptide), or one containing components that cannot be identified by amino acid sequencing, together with a corresponding "coding" peptide. Each coupling step in the assembly of the nonsequenceable compound is followed by the coupling of an amino acid to a different attachment site of the same carrier particle, whereby the amino acid unambiguously codes for the previously coupled building block of the nonsequenceable compound. The rationale is to enable the sequence determination of a biologically active compound that has been identified through the screening of a library of nonequenceable compounds, by translating the sequence of its "coding" peptide, determined by Edman degradation, into the structure of the active compound. The technique facilitates the construction and screening of nonpeptidic libraries for the discovery of important pharmaceutical compounds.
描述了一种间接确定在固体支持物的单个颗粒上合成的非肽或不可测序化合物结构的方法。该技术允许平行合成不易受埃德曼降解影响的化合物(例如N端封闭的肽),或含有不能通过氨基酸测序鉴定的成分的化合物,以及相应的“编码”肽。在不可测序化合物的组装过程中的每个偶联步骤之后,将氨基酸偶联到同一载体颗粒的不同连接位点,由此氨基酸明确地编码不可测序化合物先前偶联的构建块。其基本原理是通过将由埃德曼降解确定的其“编码”肽的序列翻译成活性化合物的结构,从而能够确定通过筛选不可测序化合物库而鉴定的生物活性化合物的序列。该技术有助于构建和筛选非肽库以发现重要的药物化合物。