Rapid biocompatible macrocyclization of peptides with decafluoro-diphenylsulfone.
Rapid biocompatible macrocyclization of peptides with decafluoro-diphenylsulfone.
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DOI：
10.1039/c5sc03856a
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发表时间：
2016-06-01
期刊：
影响因子：
8.4
通讯作者：
Derda R
中科院分区：
文献类型：
--
作者：
Kalhor-Monfared S;Jafari MR;Patterson JT;Kitov PI;Dwyer JJ;Nuss JM;Derda R
在这篇手稿中，我们描述了修饰的半胱氨酸残基的肽和蛋白质在水溶剂中通过芳香亲核取代（SNAr）与全氟芳烃（fAr）。在这篇手稿中，我们描述了修饰的半胱氨酸残基的肽和蛋白质在水溶剂中通过芳香亲核取代（SNAr）与全氟芳烃（fAr）。该反应的生物相容性使其对于由20种天然氨基酸组成的蛋白质和肽库的衍生化具有吸引力。在水性缓冲液中通过19 F NMR用模型硫醇供体（β-巯基乙醇）测量fAr衍生物的反应速率，鉴定了十氯-二苯砜（DFS）为最具反应性的SNAr亲电体。DFS与硫醇亲核试剂的反应比全氟苯的类似反应快>100 000;这种反应性的增加使得DFS能够在与生物分子和蛋白质复合物相容的水溶液中以低浓度应用，所述生物分子和蛋白质复合物被有机溶剂（例如，噬菌体）。DFS在与通用结构Xn-Cys-Xm-Cys-Xl的肽反应时形成大环，其中X是任何氨基酸并且m = 1-15。它与6种肽串-催产素、尾加压素II、鲑鱼降钙素、黑色素浓缩激素、生长抑素-14和心钠素（1-28）以及在M13噬菌体上展示的肽形成环肽。高达180 M-1 s-1的速率使该反应成为迄今为止最快的Cys修饰之一。衍生自DFS的大环化合物的长期稳定性及其对氧化的稳定性进一步支持DFS作为修饰基于肽的配体、遗传编码肽文库的环化和发现生物活性大环肽的有前景的方法。
In this manuscript, we describe modification of Cys-residues in peptides and proteins in aqueous solvents via aromatic nucleophilic substitution (SNAr) with perfluoroarenes (fAr). In this manuscript, we describe modification of Cys-residues in peptides and proteins in aqueous solvents via aromatic nucleophilic substitution (SNAr) with perfluoroarenes (fAr). Biocompatibility of this reaction makes it attractive for derivatization of proteins and peptide libraries comprised of 20 natural amino acids. Measurement of the reaction rates for fAr derivatives by 19F NMR with a model thiol donor (β-mercaptoethanol) in aqueous buffers identified decafluoro-diphenylsulfone (DFS) as the most reactive SNAr electrophile. Reaction of DFS with thiol nucleophiles is >100 000 faster than analogous reaction of perfluorobenzene; this increase in reactivity enables application of DFS at low concentrations in aqueous solutions compatible with biomolecules and protein complexes irreversibly degraded by organic solvents (e.g., bacteriophages). DFS forms macrocycles when reacted with peptides of the general structure Xn–Cys–Xm–Cys–Xl, where X is any amino acid and m = 1–15. It formed cyclic peptides with 6 peptide hormones—oxytocin, urotensin II, salmon calcitonin, melanin-concentrating hormone, somatostatin-14, and atrial natriuretic factor (1–28) as well as peptides displayed on M13 phage. Rates up to 180 M–1 s–1 make this reaction one of the fastest Cys-modifications to-date. Long-term stability of macrocycles derived from DFS and their stability toward oxidation further supports DFS as a promising method for modification of peptide-based ligands, cyclization of genetically-encoded peptide libraries, and discovery of bioactive macrocyclic peptides.
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影响因子：
15
作者：
Schlippe, Yollete V. Guillen;Hartman, Matthew C. T.;Josephson, Kristopher;Szostak, Jack W.
通讯作者：
Szostak, Jack W.
影响因子：
15
作者：
Ng S;Lin E;Kitov PI;Tjhung KF;Gerlits OO;Deng L;Kasper B;Sood A;Paschal BM;Zhang P;Ling CC;Klassen JS;Noren CJ;Mahal LK;Woods RJ;Coates L;Derda R
通讯作者：
Derda R
影响因子：
4.1
作者：
EKLADIUS, L;KING, HK
通讯作者：
KING, HK
影响因子：
4.7
作者：
Jafari, Mohammad R.;Lakusta, Jenner;Derda, Ratmir
通讯作者：
Derda, Ratmir
影响因子：
7.4
作者：
Lavis, Luke D.;Rutkoski, Thomas J.;Raines, Ronald T.
通讯作者：
Raines, Ronald T.