Gas-Phase Folding of a Prototypical Protonated Pentapeptide: Spectroscopic Evidence for Formation of a Charge-Stabilized β-Hairpin
Gas-Phase Folding of a Prototypical Protonated Pentapeptide: Spectroscopic Evidence for Formation of a Charge-Stabilized β-Hairpin
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DOI：
10.1021/jacs.6b00093
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发表时间：
2016-03-02
影响因子：
15
通讯作者：
Zwier, Timothy S.
中科院分区：
文献类型：
--
作者：
Burke, Nicole L.;DeBlase, Andrew F.;Zwier, Timothy S.
利用紫外和红外-紫外(IR-UV)双共振光碎片光谱，在串联质谱仪上测定了低温冷却质子化C-端甲基酯化亮氨酸脑啡肽[YGGFL-OME+H](+)的三维结构。通过比较主要构象的实验红外光谱与DFT M05-2X/6-31+G(D)计算的预测，指定了一个主干结构，该结构类似于我们小组以前为未修饰的多肽指定的结构[Burke，N.L.；等人]。内部J.质谱学。2015,378,196]，尽管失去了被认为在其稳定中发挥重要作用的C-末端OH结合位点。这两种结构都具有II‘型β转折Gly(3)-Phe(4)和伽马转折Gly(2)，为β-发夹氢键模式的形成提供了光谱证据。质子化的N-末端不是破坏肽的骨架结构，而是通过将自己定位在转角上方的口袋中来稳定β-发夹，在那里它可以与Gly(3)和C-末端C=0基团形成氢键。这种β-发夹型结构以前被认为是亮氨酸脑啡肽及其甲酯在非极性细胞膜环境中的生物活性构象[Naito，A.；Nishimura，K.Curr.托普。地中海医院。化学。2004，4,135-143]。
Ultraviolet and infrared-ultraviolet (IR-UV) double-resonance photofragment spectroscopy has been carried out in a tandem mass spectrometer to determine the three-dimensional structure of cryogenically cooled protonated C-terminally methyl esterified leucine enkephalin [YGGFL-OMe+H](+). By comparing the experimental IR spectrum of the dominant conformer with the predictions of DFT M05-2X/6-31+G(d) calculations, a backbone structure was assigned that is analogous to that previously assigned by our group for the unmodified peptide [Burke, N.L.; et al. Int. J. Mass Spectrom. 2015, 378, 196], despite the loss of a C-terminal OH binding site that was thought to play an important role in its stabilization. Both structures are characterized by a type II' beta-turn around Gly(3)-Phe(4) and a gamma-turn around Gly(2), providing spectroscopic evidence for the formation of a beta-hairpin hydrogen bonding pattern. Rather than disrupting the peptide backbone structure, the protonated N-terminus serves to stabilize the beta-hairpin by positioning itself in a pocket above the turn where it can form H-bonds to the Gly(3) and C-terminus C=0 groups. This beta-hairpin type structure has been previously proposed as the biologically active conformation of leucine enkephalin and its methyl ester in the nonpolar cell membrane environment [Naito, A.; Nishimura, K. Curr. Top. Med. Chem. 2004, 4, 135-143].