Dolai Gobinda, Shill Sukesh, Roy Sayanta, Mandal Bhubaneswar
Department of Chemistry, Laboratory of Peptide and Amyloid Research, Indian Institute of Technology Guwahati, Guwahati, Assam 781039, India.
Langmuir. 2023 Jul 11;39(27):9367-9383. doi: 10.1021/acs.langmuir.3c00823. Epub 2023 Jun 20.
Tryptophan (Trp) conjugates destabilize amyloid fibrils responsible for amyloidoses. However, the mechanism of such destabilization is obscure. Herein the self-assembly of four synthesized Trp-containing dipeptides Boc-xxx-Trp-OMe (xxx: Val, Leu, Ile, and Phe) has been investigated and compared with the existing report on their Phe congeners. Two among them are the C-terminal tryptophan analogs of Boc-Val-Phe-OMe (VF, Aβ) and Boc-Phe-Phe-OMe (FF, Aβ), part of the central hydrophobic region of amyloid-β (Aβ). While Boc-Val-Trp-OMe (VW), Boc-Leu-Trp-OMe (LW), Boc-Ile-Trp-OMe (IW), and Boc-Phe-Trp-OMe (FW) displayed a spherical morphology in FESEM and AFM images, the corresponding phenylalanine-containing dipeptides displayed various fibrous structures. Single-crystal X-ray diffraction (SC-XRD) indicated that peptides VW and IW exhibited structures containing parallel β-sheet, cross-β-structure, sheet-like layer structure, and helical arrangement in the solid state. Interestingly, peptide FW displayed inverse γ-turn conformation (similar to open-turn structure), antiparallel β-sheet structure, columnar structure, supramolecular nanozipper structure, sheet-like layer arrangement, and helical architecture in the solid state. The open-turn conformation and nanozipper structure formation by FW may be the first example of a dipeptide that forms such structures. The minute but consistent differences in molecular packing at the atomic level between Trp and Phe congeners may be responsible for their remarkably different supramolecular structure generation. This molecular-level structural analysis may be helpful for the design of peptide nanostructures and therapeutics. Similar studies by the Debasish Haldar group are reported, but they investigated the inhibition of fibrillization of dipeptides by tyrosine and interactions are expectedly different.
色氨酸（Trp）缀合物可使导致淀粉样变性的淀粉样纤维不稳定。然而，这种不稳定作用的机制尚不清楚。在此，我们研究了四种合成的含色氨酸二肽Boc-xxx-Trp-OMe（xxx：Val、Leu、Ile和Phe）的自组装，并将其与关于它们苯丙氨酸类似物的现有报道进行了比较。其中两种是淀粉样β蛋白（Aβ）中央疏水区域一部分的Boc-Val-Phe-OMe（VF，Aβ）和Boc-Phe-Phe-OMe（FF，Aβ）的C端色氨酸类似物。虽然Boc-Val-Trp-OMe（VW）、Boc-Leu-Trp-OMe（LW）、Boc-Ile-Trp-OMe（IW）和Boc-Phe-Trp-OMe（FW）在场发射扫描电子显微镜（FESEM）和原子力显微镜（AFM）图像中呈现球形形态，但相应的含苯丙氨酸二肽呈现出各种纤维结构。单晶X射线衍射（SC-XRD）表明，肽VW和IW在固态下呈现出包含平行β-折叠、交叉β-结构、片状层结构和螺旋排列的结构。有趣的是，肽FW在固态下呈现出反向γ-转角构象（类似于开放转角结构）、反平行β-折叠结构、柱状结构、超分子纳米拉链结构、片状层排列和螺旋结构。FW形成的开放转角构象和纳米拉链结构可能是形成此类结构的二肽的首个例子。色氨酸和苯丙氨酸类似物在原子水平上分子堆积的微小但一致的差异可能是它们产生显著不同的超分子结构的原因。这种分子水平的结构分析可能有助于肽纳米结构的设计和治疗。Debasish Haldar团队也报道了类似的研究，但他们研究的是酪氨酸对二肽纤维化的抑制作用，预计相互作用会有所不同。
