4R- and 4S-iodophenyl hydroxyproline, 4R-pentynoyl hydroxyproline, and S-propargyl-4-thiolphenylalanine: conformationally biased and tunable amino acids for bioorthogonal reactions.
4R- and 4S-iodophenyl hydroxyproline, 4R-pentynoyl hydroxyproline, and S-propargyl-4-thiolphenylalanine: conformationally biased and tunable amino acids for bioorthogonal reactions.
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DOI：
10.1039/c5ob02473k
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发表时间：
2016-02-21
影响因子：
3.2
通讯作者：
Zondlo NJ
中科院分区：
文献类型：
--
作者：
Forbes CR;Pandey AK;Ganguly HK;Yap GP;Zondlo NJ
生物正交反应允许将新功能引入肽、蛋白质和其他生物分子。生物正交反应中最容易获得的氨基酸具有适度的构象偏好或分子相互作用的基础。在此，我们描述了4个新的氨基酸含有功能基团的生物正交反应的合成。(2S羟脯氨酸的（2S，4S）-和（4R）-碘苯基醚能够通过在水中的快速、特异性Suzuki和Sonogashira反应进行修饰。这些氨基酸的合成，如Boc-，Fmoc-和游离氨基酸，通过简洁的序列实现。这些氨基酸显示出明确的构象偏好，4S-碘苯基羟脯氨酸在晶体学上显示出β-转角（β，β~− 80 °，0 °）或相对延伸的（β，β~− 80 °，+170 °）构象，而4R-非对映异构体更喜欢更紧凑的构象（β~− 60 °）。芳氧基脯氨酸的非对映异构体目前的芳基基团在一个高度发散的方式，表明它们的立体定向使用的分子设计，药物化学和催化。因此，4R-和4S-碘苯基羟基脯氨酸可以在不同的结构背景下有区别地应用。4R-羟基脯氨酸的戊炔酸酯在氨基酸内引入了优选紧凑构象的炔官能团。以硫代乙酸和保护的4-碘苯丙氨酸为原料，经铜离子催化偶联、硫解、烷基化反应合成了4-巯基苯丙氨酸炔丙基硫醚。这种氨基酸将炔官能团与芳香族氨基酸结合，并具有通过硫氧化调节芳香族和侧链性质的能力。这些氨基酸为肽功能化提供了新的位点，与含有这些官能团的其他氨基酸相比，可以更好地控制构象。
Bioorthogonal reactions allow the introduction of new functionalities into peptides, proteins, and other biological molecules. The most readily accessible amino acids for biooorthogonal reactions have modest conformational preferences or bases for molecular interactions. Herein we describe the synthesis of 4 novel amino acids containing functional groups for bioorthogonal reactions. (2S,4R)- and (2S,4S)-iodophenyl ethers of hydroxyproline are capable of modification via rapid, specific Suzuki and Sonogashira reactions in water. The synthesis of these amino acids, as Boc-, Fmoc- and free amino acids, was achieved through succinct sequences. These amino acids exhibit well-defined conformational preferences, with the 4S-iodophenyl hydroxyproline crystallographically exhibiting β-turn (ϕ, ψ ~ −80°, 0°) or relatively extended (ϕ, ψ ~ −80°, +170°) conformations, while the 4R- diastereomer prefers a more compact conformation (ϕ ~ −60°). The aryloxyproline diastereomers present the aryl groups in a highly divergent manner, suggesting their stereospecific use in molecular design, medicinal chemistry, and catalysis. Thus, the 4R- and 4S-iodophenyl hydroxyprolines can be differentially applied in distinct structural contexts. The pentynoate ester of 4R-hydroxyproline introduces an alkyne functional group within an amino acid that prefers compact conformations. The propargyl thioether of 4-thiolphenylalanine was synthesized via copper-mediated cross-coupling reaction of thioacetic acid with protected 4-iodophenylalanine, followed by thiolysis and alkylation. This amino acid combines an alkyne functional group with an aromatic amino acid and the ability to tune aromatic and side chain properties via sulfur oxidation. These amino acids provide novel loci for peptide functionalization, with greater control of conformation possible than with other amino acids containing these functional groups.
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影响因子：
15
作者：
Blackman, Melissa L.;Royzen, Maksim;Fox, Joseph M.
通讯作者：
Fox, Joseph M.
影响因子：
15
作者：
DeRider, ML;Wilkens, SJ;Markley, JL
通讯作者：
Markley, JL
影响因子：
3.6
作者：
Brunner, Henri;Tsuno, Takashi;Bodensteiner, Michael
通讯作者：
Bodensteiner, Michael
影响因子：
56.9
作者：
DAWSON, PE;MUIR, TW;KENT, SBH
通讯作者：
KENT, SBH
影响因子：
15
作者：
Bretscher, LE;Jenkins, CL;Raines, RT
通讯作者：
Raines, RT