Cleavage kinetics and anchor linked intermediates in solid phase peptide amide synthesis.
Cleavage kinetics and anchor linked intermediates in solid phase peptide amide synthesis.
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固相肽酰胺合成中的裂解动力学和锚定连接中间体。
DOI：
10.1111/j.1399-3011.1991.tb01422.x
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
G. Jung
中科院分区：
文献类型：
--
作者：
H. Dürr;A. Beck‐Sickinger;G. Schnorrenberg;W. Rapp;G. Jung
研究了以5-（4 '-氨甲基-3'，5 '-二甲氧基苯氧基）戊酸（4-ADPV-OH）和5-（2'-氨甲基-3 '-5'-二甲氧基苯氧基）戊酸（2-ADPV-OH）为锚分子合成肽酰胺的动力学和裂解条件。出乎意料的是，在用三氟乙酸（TFA）裂解丙氨酰-4-ADPV-丙氨酰-氨甲基-聚苯乙烯以产生丙氨酸酰胺的过程中，分离出了锚酰胺丙氨酰-4-ADPV-NH 2，并将其表征为中间体。事实上，丙氨酰间隔基的NH-CH α键必须裂解以形成该中间体。使用TFA-二氯甲烷（1：9），在60分钟内以50%产率获得作为裂解产物的丙氨酰-4-ADPV-NH 2，而异构体丙氨酰-2-ADPV-NH 2在这些温和条件下形成得更慢。在高TFA浓度下，2-和4-ADPV锚之间在游离丙氨酸酰胺的形成速率方面没有观察到差异。色氨酸酰胺在裂解混合物中的存在导致锚烷基化色氨酸酰胺，其在酸性溶液中保持稳定，但在树脂存在下迅速消失。推荐低TFA/高TFA裂解程序用于应用ADPV锚的肽酰胺合成。
Kinetics and cleavage conditions of peptide amide synthesis were studied using the anchor molecules 5-(4'-aminomethyl-3',5'-dimethoxyphenoxy)valeric acid (4-ADPV-OH) and 5-(2'-aminomethyl-3'-5'-dimethoxyphenoxy) valeric acid (2-ADPV-OH). Unexpectedly the anchor amide alanyl-4-ADPV-NH2 was isolated and characterized as an intermediate during the cleavage with trifluoroacetic acid (TFA) of alanyl-4-ADPV-alanyl-aminomethyl-polystyrene to yield the alanine amide. As a matter of fact the NH--CH alpha bond of the alanyl spacer has to be cleaved to form this intermediate. Using TFA-dichloromethane (1:9) alanyl-4-ADPV-NH2 was obtained as a cleavage product in 50% yield within 60 min, whereas the isomeric alanyl-2-ADPV-NH2 was formed more slowly under these mild conditions. At high TFA concentration no difference between the 2- and 4-ADPV anchor was observed in the rate of formation of the free alanine amide. The presence of tryptophan amide in the cleavage mixture resulted in an anchor alkylated tryptophan amide, which remains stable in acidic solution but disappears rapidly in the presence of the resin. A low TFA/high TFA cleavage procedure is recommended for peptide amid synthesis applying the ADPV anchor.
用于在温和条件下固相合成 C 端肽酰胺的酸不稳定锚定键。
DOI：
10.1111/j.1399-3011.1987.tb03328.x
发表时间：
1987
期刊：
International journal of peptide and protein research
影响因子：
--
作者：
Albericio,F;Barany,G
通讯作者：
Barany,G