Dörner B, Husar G M, Ostresh J M, Houghten R A
Torrey Pines Institute for Molecular Studies, San Diego, CA 92121, USA.
Bioorg Med Chem. 1996 May;4(5):709-15. doi: 10.1016/0968-0896(96)00067-3.
A soluble peptidomimetic combinatorial library of 57,500 compounds was prepared. This library has a dipeptide scaffold with each amide hydrogen replaced with five different alkyl groups (methyl, ethyl, allyl, benzyl, or naphthylmethyl). Solid-phase methodology in combination with N-alkylation were used to synthesize the library, which incorporated 50 different L-, D-, and unnatural amino acids. Repetitive amide alkylations were carried out on the solid support following each amino acid coupling step. Individual model compounds were synthesized in order to optimize the alkylation conditions, to study potential amino acid side chain modifications, to determine the extent of racemization, and to provide analytical controls during the library synthesis.
制备了一个包含57,500种化合物的可溶性拟肽组合文库。该文库具有二肽骨架，每个酰胺氢被五个不同的烷基（甲基、乙基、烯丙基、苄基或萘甲基）取代。采用固相方法结合N-烷基化来合成该文库，其中包含50种不同的L-、D-和非天然氨基酸。在每个氨基酸偶联步骤之后，在固相载体上进行重复的酰胺烷基化反应。合成了单个模型化合物，以优化烷基化条件、研究潜在的氨基酸侧链修饰、确定消旋化程度，并在文库合成过程中提供分析对照。
