3-硝基-2-吡啶亚磺酰基保护基在固相肽合成过程中在赖氨酸上引入Nε-支化的用途I.在包含两个可寻址位点的肽模板的合成中的应用,Chemical Biology & Drug Design

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3-硝基-2-吡啶亚磺酰基保护基在固相肽合成过程中在赖氨酸上引入Nε-支化的用途I.在包含两个可寻址位点的肽模板的合成中的应用
Chemical Biology & Drug Design ( IF 3.2 ) Pub Date : 2009-01-12 , DOI: 10.1111/j.1399-3011.1995.tb01037.x
SHYAMALA RAJAGOPALAN , THOMAS J. HECK , TAKEO IWAMOTO , JOHN M. TOMICH

TASP（模板组装的合成肽）是通过线性肽与普通肽主链的共价连接产生的，从而生成具有预折叠结构的更大的合成肽/蛋白质。在这项工作中，我们提出了一种策略，用于合成包含两个可寻址位点的异模板组装的合成肽。这种正交保护策略将允许通过赖氨酸甲氧基羰基（Fmoc）或3-硝基-2-吡啶亚磺酰基（Npys）基团保护的模板赖氨酸的ε-氨基官能团选择性引入不同的肽链。固相肽合成（SPPS）所需的N alpha-Boc-N epsilon-Npys-L-赖氨酸尚无法以合理的价格获得。为了促进该试剂的更广泛使用，我们比较了两种公开的合成该受保护氨基酸的程序，并评估了该产品对SPPS的适用性。通过SPPS合成了两个树脂结合肽，即三肽Ac-GK-Npys-G-树脂和八肽模板Ac-P1-K2-K3-L4-K5-K6-P7-G8-树脂。八肽的赖氨酸K2和K6以及K3和K5的ε-氨基官能团分别被Fmoc和Npys基团保护。其次，这些肽用于评估各种试剂和反应条件，以使带有N epsilon-Npys保护基的赖氨酸的ε-氨基功能脱保护。

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Use of the 3-nitro-2-pyridine sulfenyl protecting group to introduce Nε-branching at lysine during solid-phase peptide synthesis I. Application to the synthesis of a peptide template containing two addressable sites

TASPs (template-assembled synthetic peptides) are generated by the covalent attachment of linear peptides to a common peptide backbone, thus generating larger synthetic peptides/proteins with prefolded structure. In this work we present a strategy for the synthesis of a heterotemplate-assembled synthetic peptide containing two addressable sites. This orthogonal protection strategy would allow the selective introduction of different peptide chains via the epsilon-amino functions of template lysines being protected by either fluorenylmethoxycarbonyl (Fmoc) or 3-nitro-2-pyridine sulfenyl (Npys) groups. The N alpha-Boc-N epsilon-Npys-L-lysine required for solid-phase peptide synthesis (SPPS) is not readily available at a reasonable cost. To facilitate the more widespread use of this reagent we have compared the two published procedures for synthesizing this protected amino acid and evaluated the suitability of the products for SPPS. Two resin-bound peptides, a tripeptide Ac-G-K-Npys)-G-resin and an octapeptide template Ac-P1-K2-K3-L4-K5-K6-P7-G8-resin, were synthesized by SPPS. The epsilon-amino functions of lysines K2 & K6 and K3 & K5 of the octapeptide were protected by Fmoc and Npys groups, respectively. Secondly, these peptides were used to evaluate various reagents and reaction conditions for the deprotection of the epsilon-amino function of lysines bearing the N epsilon-Npys protecting group. A procedure for the optimized selective and quantitative deprotection of the Npys group from the epsilon-amino function of lysine in a resin-bound peptide using 2-mercaptopyridine-N-oxide is described.

更新日期：2009-01-12

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