Peptide Self-Assembly and Engineering E-Book

• Herausgeber: Wiley-VCH GmbH
• Kategorie: Wissenschaft und neue Technologien
• Sprache: Englisch
• Veröffentlichungsjahr: 2024

Seitenzahl: 1246

Beschreibung

A very comprehensive reference covers the latest progresses in the field of Peptide Self-Assembly and Engineering.

Das E-Book Peptide Self-Assembly and Engineering wird angeboten von Wiley-VCH GmbH und wurde mit folgenden Begriffen kategorisiert:
Biomolecules (DNA, RNA, Peptides, etc.), Biomolekül, Biomoleküle, Biomoleküle (DNA, RNA, Peptide), Chemie, Chemistry, Nanomaterialien, Nanomaterials, Nanotechnologie, Nanotechnology, Pharmaceutical & Medicinal Chemistry, Pharmazeutische u. Medizinische Chemie

Leseprobe

Peptide Self‐Assembly and Engineering

Fundamentals, Structures, and Applications

Volume 1

Edited by Xuehai Yan

Peptide Self-Assembly and Engineering

Fundamentals, Structures, and Applications

Volume 2

Edited by Xuehai Yan

Editor

Prof. Xuehai YanInstitute of Process Engineering, CASZhongguancunHaidian DistrictBeijing, 100190China

Cover Image: © Xuehai Yan

All books published by WILEY‐VCH are carefully produced. Nevertheless, authors, editors, and publisher do not warrant the information contained in these books, including this book, to be free of errors. Readers are advised to keep in mind that statements, data, illustrations, procedural details or other items may inadvertently be inaccurate.

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© 2024 Wiley‐VCH GmbH, Boschstraße 12, 69469 Weinheim, Germany

All rights reserved (including those of translation into other languages). No part of this book may be reproduced in any form – by photoprinting, microfilm, or any other means – nor transmitted or translated into a machine language without written permission from the publishers. Registered names, trademarks, etc. used in this book, even when not specifically marked as such, are not to be considered unprotected by law.

Print ISBN: 978‐3‐527‐35195‐4ePDF ISBN: 978‐3‐527‐84124‐0ePub ISBN: 978‐3‐527‐84125‐7oBook ISBN: 978‐3‐527‐84126‐4

Editor

Prof. Xuehai YanInstitute of Process Engineering, CASZhongguancunHaidian DistrictBeijing, 100190China

Cover Image: © Xuehai Yan

All books published by WILEY‐VCH are carefully produced. Nevertheless, authors, editors, and publisher do not warrant the information contained in these books, including this book, to be free of errors. Readers are advised to keep in mind that statements, data, illustrations, procedural details or other items may inadvertently be inaccurate.

Library of Congress Card No.: applied for

British Library Cataloguing‐in‐Publication DataA catalogue record for this book is available from the British Library.

Bibliographic information published by the Deutsche NationalbibliothekThe Deutsche Nationalbibliothek lists this publication in the Deutsche Nationalbibliografie; detailed bibliographic data are available on the Internet at http://dnb.d-nb.de.

© 2024 Wiley‐VCH GmbH, Boschstraße 12, 69469 Weinheim, Germany

All rights reserved (including those of translation into other languages). No part of this book may be reproduced in any form – by photoprinting, microfilm, or any other means – nor transmitted or translated into a machine language without written permission from the publishers. Registered names, trademarks, etc. used in this book, even when not specifically marked as such, are not to be considered unprotected by law.

Print ISBN: 978‐3‐527‐35196‐1ePDF ISBN: 978‐3‐527‐84124‐0ePub ISBN: 978‐3‐527‐84125‐7oBook ISBN: 978‐3‐527‐84126‐4

Preface

It is with great pleasure that I introduce this book, which marks the 30th anniversary of the discovery of the first peptide building block capable of self‐assembly. Over the past three decades, this field has undergone remarkable growth in scientific understanding and technical expertise. The materials and techniques derived from this research have not only expanded our knowledge but also provided us with innovative tools to address the challenges faced in the development of our modern society. The use of peptide‐based materials with biocompatibility, biodegradability, and biorecyclability holds immense potential for promoting healthy, green and sustainable development on our planet.

In celebration of this significant milestone, I propose the publication of a comprehensive book that provides an overview of the advancements and future directions in peptide self‐assembly and engineering. One particularly captivating area of exploration is the recent discovery of amino acid and peptide glasses, which exist in a thermodynamically metastable state. This finding opens up exciting avenues for the creation of dynamic, complex, and metastable glassy structures and materials that closely resemble biological systems. I firmly believe that more fascinating discoveries and groundbreaking achievements in the field of peptide self‐assembly and engineering are yet to come, making this an ideal time to compile a book that presents a summary of the latest scientific findings from the past decades.

This book covers a wide range of topics related to peptide self‐assembly and engineering, including self‐assembly principles, assembled structures and functions, and materials engineering and applications. As such, it will cater to a diverse readership, comprising individuals with backgrounds in chemistry, materials science, nanotechnology, molecular engineering, biomedicine, and life science. Whether you come from academia, industry, or the education sector, I am confident that you will find valuable insights and information within the pages of this book.

Finally, I would like to express my deepest gratitude to my mentors, colleagues, collaborators, and students, as well as family members, whose unwavering support has been instrumental in my academic journey. I extend my heartfelt appreciation to the contributors of each chapter for accepting my invitation and sharing their expertise to make this book a reality.

Xuehai YanBeijing, ChinaAugust 2023

1Introduction to the Concept, History, and Significance of Peptide Self‐assembly and Materials

Xuehai Yan

State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, No.1 North 2nd Street, Zhongguancun, Haidian District, Beijing, P. R. China

University of Chinese Academy of Sciences, School of Chemical Engineering, No.1 Yanqihu East Rd, Huairou District, Beijing, P. R. China

Center for Mesoscience, Institute of Process Engineering, Chinese Academy of Sciences, No.1 North 2nd Street, Zhongguancun, Haidian District, Beijing, P. R. China

Self‐assembly is a ubiquitous phenomenon in nature. Biological molecules such as phospholipid, protein, and DNA can undergo hierarchical and multiscale self‐assembly to form complex and dynamic architectures and ultimately cells with life activities [1, 2]. Over the past few decades, extreme efforts have been made to design and develop self‐assembling biomolecular building blocks so as to obtain biologically based materials with structures and functions similar to the natural ones.

Peptides typically comprise 2–50 amino acids and are as a structural motif of proteins. Due to their availability, programmability, biocompatibility, and biodegradability, peptides have been recognized as a kind of popular and promising molecular building blocks for fabrication of well‐ordered nanostructures and functional materials [3–5]. Hence, the study of peptide self‐assembly and engineering not only enriches biologically based materials with abundant structures and functions but also contributes to a broad range of applications from energy conversion to disease treatments.

The history of peptide self‐assembly for design of functional materials can be traced back to the early 1990s. In 1993, Ghadiri and coworkers experimentally demonstrated the assembly of cyclic peptides containing alternating D‐ and L‐amino acids, resulting in a new class of hollow nanotubes [6] that were originally predicted by De Santis et al. In the same year, Zhang and coworkers discovered the repetitious and ionic self‐complementary peptide segment in yeast protein Zuotin [7]. Such ionic complementary peptides were found to spontaneously form ordered nanofibers through noncovalent interactions. After that, a variety of peptides with diverse secondary structures of β‐sheets [8], β‐hairpins [9], α‐helices [10], and coiled coils [11] are developed as building blocks for preparation of soft materials such as supramolecular hydrogels. In 2001, Stupp and coworkers developed a family of peptide amphiphile (PA) as characterized by a hydrophilic peptide head modified with a hydrophobic alkyl tail [12, 13]. Such a design allows for the flexible incorporation of functional peptide sequence into the end of PA that usually displays biological functions. The discovery of the nanotube‐forming aromatic diphenylalanine [14], the core recognition motif of Alzheimer's β‐amyloid, stimulates a passion to explore short peptides consisting of 2–3 amino acids for self‐assembly. With the motivation of integrating multiple functions into the peptide‐based materials, a series of chromopeptides that combine peptide motifs and chromophores, similar to chromoproteins, are developed as building blocks [15, 16]. The chromopeptides can self‐assemble to form a variety of architectures with both biofunctions and photofunctions.

Nowadays, peptide self‐assembly has been a subject of intensive research for both fundamental and applied aims due to its customizability and superiority based on the “bottom‐up” methodology. Peptide self‐assembly is a process that associates with noncovalent interactions, such as hydrogen bonds, hydrophobic interactions, van der Waals forces, and electrostatic forces [17]. This process can lead to the formation of a variety of nanostructures, ranging from simple nanoparticles and nanofibers to more complex hierarchical structures such as microtubes, microwires, and capsules. Understanding the fundamental principles that guide peptide self‐assembly, particularly the intermolecular interactions and multiscale dynamic processes, is critical to engineering peptide‐based materials [17–19]. In recent years, there have been numerous innovative strategies developed to precisely regulate the structures and functions of peptide assemblies, thus leading to the development of peptide‐based functional materials for various applications.

Molecular peptide design is a crucial factor that determines the properties and functions of peptide assemblies, and it involves a balance between structural stability and functional performance [20, 21]. To achieve the desired properties and functions, various factors such as charge, hydrophobicity, and secondary structure must be rationally considered in the design of molecular peptide building blocks. The solvent environment also plays a critical role in peptide self‐assembly, and various solvent conditions such as pH, ionic strength, and polarity can affect the structure and stability of peptide assemblies. Different solvent conditions can lead to changes in the intermolecular interactions between peptides, affecting their ability to self‐assemble and ultimately impacting their structures and functions. Computational simulations, such as molecular dynamics, have become essential tools for investigating the thermodynamics and kinetics of peptide self‐assembly at the molecular level [22]. Using the computational methods, researchers can well optimize peptide design and solvent conditions to achieve the desired structures and properties of the resulting assemblies.

Peptide self‐assembly enables the generation of nanostructured materials with unique and useful properties that have expanded their applications in fields such as biomedical engineering, nanotechnology, and photoelectronics. These materials possess unique mechanical, optical, electronic, and biological properties that make them highly suitable for developing new materials. For instance, self‐assembled peptide materials have been used for tissue engineering, drug delivery, and biosensing devices due to their biocompatibility and ability to mimic natural extracellular matrices. Overall, peptide self‐assembly has opened up new opportunities for developing next‐generation green and eco‐friendly materials and technique toward a sustainable future [23].

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Ghadiri, M., Granja, J., Milligan, R. et al. (1993). Self‐assembling organic nanotubes based on a cyclic peptide architecture.

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Zhang, S., Holmes, T., Lockshin, C., and Rich, A. (1993). Spontaneous assembly of a self‐complementary oligopeptide to form a stable macroscopic membrane.

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Yokoi, H., Kinoshita, T., and Zhang, S. (2005). Dynamic reassembly of peptide RADA16 nanofiber scaffold.

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Schneider, J., Pochan, D., Ozbas, B. et al. (2002). Responsive hydrogels from the intramolecular folding and self‐assembly of a designed peptide.

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Ogihara, N., Ghirlanda, G., Bryson, J. et al. (2001). Design of three‐dimensional domain‐swapped dimers and fibrous oligomers.

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Pandya, M., Spooner, G., Sunde, M. et al. (2000). Sticky‐end assembly of a designed peptide fiber provides insight into protein fibrillogenesis.

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Cui, H., Webber, M., and Stupp, S. (2010). Self‐assembly of peptide amphiphiles: from molecules to nanostructures to biomaterials.

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Reche, M. and Gazit, E. (2003). Casting metal nanowires within discrete self‐assembled peptide nanotubes.

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Zou, Q., Zhang, L., Yan, X. et al. (2014). Multi‐functional porous microspheres based on peptide‐porphyrin hierarchical co‐assembly.

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Chang, R., Zhao, L., Xing, R. et al. (2023). Functional chromopeptide nanoarchitectonics: molecular design, self‐assembly and biological applications.

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Yuan, C., Ji, W., Xing, R. et al. (2019). Hierarchically oriented organization in supramolecular peptide crystals.

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2Peptides: Molecular Basis, Secondary Structures, and Synthesis Methods

Luyang Zhao1, Xiaokang Ren1,2, and Xuehai Yan1,2,3

1 State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China

2 School of Chemical Engineering, University of Chinese Academy of Sciences, Beijing 100049, China

3 Center for Mesoscience, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China

2.1 Molecular Basis of Peptides

Peptides are short chains of covalently‐linked amino acids. The amino acids are joined by an amide linkage, also called peptide bond. Peptides can be crudely classified as oligo‐ and polypeptides, depending on the number of joined amino acids. Oligopeptides are formed if a few amino acids are joined together, while polypeptides are formed if many amino acids are joined into one chain. Peptides contain only one free α‐amino group and one free α‐carboxylic group located on the two terminals of the peptide chain, respectively. These two terminal groups together with the polar groups of the amino‐acid residues amid the peptide chain may ionize to charged groups in aqueous media. This leads to the acid–base behavior with characteristic titration curves and characteristic isoelectric pH (pI). Of course, the ionization makes peptides pH‐responsive and property‐variable in certain conditions.

Naturally occurring peptides are widely distributed in living organisms with diverse functions. The amino‐acid residues of natural peptides range in quantities from two to many thousands. It is interesting that even the shortest peptides may have important biological effects. A typical example is the aspartylphenylalanine methyl ester, a commercially available dipeptide (ester derivative) known as aspartame that is used as a sugar substitute in foods and beverages. Many peptides represent their functions at very low concentrations. For example, a number of vertebrate hormones include oxytocin (a nonapeptide), which is released by the posterior pituitary and stimulates uterine contractions. Thyrotropin‐releasing factor, a tripeptide that is formed in the hypothalamus, stimulates the release of thyrotropin, another hormone from the anterior pituitary gland. Some highly toxic mushroom poisons, such as amanitin, are also small peptides like many antibiotics.

Inspired by the great values of peptides, scientists designed peptide sequences that are not found in nature. These are classified as artificial peptides. Artificial peptides differ from naturally occurring peptides in both structure and functionality. Artificial peptides may also include nonnatural amino‐acid residues or derived peptide backbone. It is well known that there are 20 common amino acids, while nonnatural amino acids that have been reported thus far exceed more than 300 [1–3]. Besides, the basic peptide backbone skeleton may be arbitrarily modified or inserted by external groups. Therefore, the space for peptide and peptide derivative construction is dimensionless. The artificial peptides are applied not only on biological processes as substitutes with optimized properties to natural peptides but also expanded to therapeutics, drug delivery, catalysis, and so forth [4–7].

2.2 Peptide Secondary Structures

The key difference between peptides and proteins is that the former do not possess tertiary structure. However, peptides own secondary structures, and this is usually crucial for peptide assembly and many other properties. Naturally occurring peptide secondary structures may be divided into three kinds: helices, sheets, and turns. Each kind includes several subtypes, depending on the peptide backbone skeleton. As shown in Figure 2.1, other than the planar conformation of amide bond, the backbone orientation around the Cα atom of each amino‐acid residue of the peptide has rotational freedom and leads to the flexible peptide chain. The orientation is described by two dihedral angles concerning the Cα atom, namely φ(Ci − 1−Ni−Cα,i−Ci) and ψ(Ni−Cα,i−Ci−Ni + 1). The combination of these two angles gives rise to a certain peptide secondary structure and is feasibly revealed by the Ramachandran plot [8].

Figure 2.1 Peptide structure and stereo representation.

The secondary structure of peptides is partially influenced by intra‐ or intermolecular interactions including electrostatic interaction, hydrogen‐bonding (HB) interaction, hydrophobic interaction, and van de Waals (VdW) interaction. Although these interactions are not exclusive to one another, for instance HB interaction contains electrostatic interaction because the electronegative atoms and hydrogen among one HB group are charged [9], they well depict the peptide structure variation in most cases, which will be detailed below. On the other hand, the secondary structure is also affected by the amino‐acid residues, especially their spatial arrangement neighboring to each other. If these steric effects are repetitively arranged (and this occurs in many cases), periodic helices and sheets will be formed [10]. Especially, the adjacent Cα atoms with identical or similar dihedral angles play a vital role in the structural periodicity.

Nowadays, it is widely believed that the peptide and protein structures are determined solely by the primary amino‐acid sequence. This is because the sequentially connected amino acids provide two approaches of influences with the backbone: (i) the steric effects of side chains require that the number of amide H‐bonds be reduced, and (ii) the side chains have various weak interactions with backbone or other side‐chain groups [11, 12]. Following the hypothesis, much effort was paid to predict the secondary or higher level structures of peptides or proteins via the primary sequence. However, a few works denoted that the secondary structure can be tuned by thermodynamic conditions such as temperature, solvent pH, and ionic strength [13–15], which means that the evolution from a randomized structure is not unique and may lead to different secondary structures along with different pathways [16–18]. The multiple pathways appended more complexity to the peptide secondary structure and are extremely important for peptide assembly.

2.2.1 Helices

Helices are the most common secondary structures distinguished by the intramolecular hydrogen bonding patterns. α‐Helix is featured by the hydrogen‐bonding interaction between the CO and NH groups of the amino acids indexed by i and i + 4, respectively, on the backbone, which is briefly denoted as COi ← HNi+4. This means four residues apart in the sequence [19]. Such an intra‐backbone H‐bonding pattern gives rise to a helical turn with 3.6 amino acids per turn, and the amino acids in a linear sequence are spatially far apart in spatial proximity. In nature, due to the chiral L‐configuration of amino acids, clockwise arrangement is energetically superior to counterclockwise arrangement in a supramolecular assembly structure with low steric hindrance.

310‐Helix is featured by the H‐bonds between the amino‐acid residues indexed by i and i + 3 and denoted as COi ← HNi+3, which leads to three residues per turn [20]. However, 310‐helix owns a more stretched structure than that of the α‐helix (Figure 2.2a) and has 10 atoms in the turn formed by making the H‐bond. Each amino acid in the 310 helix corresponds to a 120° turn and a translation of 2.0 Å along the helical axis. Residues in long 310‐helices adopt (φ, ψ) dihedral angles near (−49°, −26°), but the value is usually deviated because 310‐helices are normally shorter than α‐helices.

The third type is π‐type helix, which is featured by a COi ← HNi+5 H‐bond pattern and 4.4 residues per turn (Figure 2.2a) [21]. The standard π‐helix is right‐handed with 4.1 residues per turn, corresponding to an 87° turn for each amino acid and a translation of 1.15 Å along the helical axis. It is much smaller than the other two types of helices, usually containing no more than seven residues in length. Consequently, its regular repeats have much fewer dihedral angles than the other two types of helices.

Figure 2.2 Main peptide secondary structure models. (a) Helices, including 310‐helix (PDB ID: 7QDI), α‐helix (PDB ID: 111L), and π‐helix (PDB ID: 1X38); (b) sheets, including parallel β‐sheet (PDB ID: 2BEG) and antiparallel β‐sheet (PDB ID: 2TRX); (c) turns, including β‐turn (PDB ID: 1N09) and inversed γ‐turn (PDB ID: 2EW4).

Source: Adapted with permission from Ref. [10]. Copyright 2020 American Chemical Society.

These naturally occurring helical structures stimulated researchers to explore hitherto unseen structures with spectacular functions. Nam et al. identified a pentapeptide sequenced by YFCFY that can fold to helix via the formation of disulfide bond and further assemble into macroscopic flat sheets at the air/water interface [22]. The pentapeptide can be prolonged to a heptapeptide with YYACAYY sequence and the mutation of F to A [23], which exhibited unambiguous α‐helix according to single‐crystal characterization. The formation of α‐helix also underwent the formation of disulfide bond which is oxidized by silver ion. This peptide template is expected to facilitate efficient electron transfer to improve the electrochemical properties.

In many cases, α‐helical peptides have considerably long sequence. Researchers deciphered the sequence code to construct self‐assembling α‐helical peptides. The key strategy is to construct a helix based on the heptad repeat sequence abcdefg, with the a, d, e, and g positions responsible for directing the generation of interhelical dimers or multimers (Figure 2.3) [26]. The dimers are combined via hydrophobic interactions between the apolar amino‐acid residues from each monomer at the specific sites. On this basis, the self‐assembling behavior of peptides could be regulated by mutating the amino‐acid residues. Adams et al. for the first time reported self‐assembling hydrogels based on the purely α‐helical linear peptides [27]. They designed a series of peptides encoded by IXXLKXK IXXLKXE IXXLEXE NXXLEX, where X is either A or Q. The peptides formed α‐helical fibril arrays and interacted with each other to form hydrogels supporting >99% water content. They showed an intriguing property that gelled only by mixing, so that their formation or assembly could be rigorously controlled. Such a property rendered the α‐helical peptides to be applied as substrates in cell cultivation, which was found to promote the growth and differentiation of pheochromocytoma cells.

Figure 2.3 (a) Helical wheel representation of the repeated heptad of coiled‐coil sequence. The helical dimers are formed due to the hydrophobic interactions on a and d sites. (b) Top view of an coiled‐coil dimer crystal structure (PDB ID: 4DZM) [24].

Source: Reprinted with permission Ref. [25]. Copyright 2019, John Wiley & Sons.

In addition to the fibrils, Woolfson and Thomson et al. developed a geometrical framework for constructing α‐helical barrels based on α‐helical peptides and their complex assembly pattern, known as coiled‐coil packing [28]. The unit of these de novo designed barrels showed near‐parallel oligomeric structures, which expand the rationally designed coiled‐coil assemblies from commonly prepared dimer to heptamer. Such coiled‐coil oligomers could be applied as fluorescence label of proteins and to mimic diverse biological enzymatic reactions such as peptide ligation, transfer reactions, and redox reactions [25].

2.2.2 Sheets

β‐Sheets describe the secondary structure that the peptide amide bonds are arranged in‐plane like a pleated sheet [29]. In the β‐sheet structure, the stretched polypeptide chains, called β‐strands, are extended into a zigzag pattern by a series of sequential interstrand H‐bonds rather than helical structure. The adjacent β‐strands that form a β‐sheet may be either parallel or antiparallel (Figure 2.2b). They have a similar structure, with a repeat period of 6.5 Å for the parallel conformation and a slightly longer period of 7.0 Å for the antiparallel conformation. They also have the same dihedral angles φ and ψ. The difference lies on their hydrogen‐bonding patterns, where the hydrogen bonds of the antiparallel conformation adopt an alternating sequence of 10‐ and 14‐membered rings. In contrast, the hydrogen bonds in the parallel conformation always consist of 12‐membered rings. These similarities lead to the possibility that multistrand β‐sheet structures may contain either purely parallel or antiparallel features or a mixture of both.

Naturally occurring β‐sheet structures are like native silk protein [30] or immunoglobulins [31]. β‐Sheet structures are also observed in certain diseases such as neurodegenerative diseases [32]. Inspired by the naturally existing peptide β‐sheets, researchers explored various protocols for constructing artificial ones. One of the successfully developed design is that of the ionic‐complementary peptides, which are characterized by the alternating arrangement of negatively and positively charged amino‐acid residues. The ionic‐complementary peptides contain the sequence segments typically such as –AEAEAKAK– and –RIQIRIQI [33, 34]. Their hydrophilic and ‐phobic regions are arranged alternately and divided into two ordered regions. The hydrophobic amino‐acid residues are folded to shield water molecules, and the hydrophilic region has regular and orderly positive and negative charges to attract each other. The formation of intermolecular hydrogen bonds accelerated the self‐assembly of peptides, and the mutual chimerism of ionic bonds increased the strength of self‐assembled structures. It is worth noting that β‐sheets are not always flat, and twisted β‐sheets in a right‐handed fashion are found in proteins [35]. Especially, a slight structural deviation from flat β‐sheet may lead to drastically different self‐assembly structure [36].

In addition, β‐sheets may form a β‐sandwich when stacked together through hydrophobic face‐to‐face interactions. β‐Sandwiches are widely found in protein domains and can assemble and lead to unique quaternary structure and function. β‐Sheets may also stack to form enclosed structures without exposing hydrogen‐bonding edges, called β‐barrels. Small β‐barrels are structurally similar to β‐sandwiches, with the neighboring layer edges being hydrogen‐bonded. Comparably, large β‐barrels typically form cavities accommodating with additional molecule or molecular groups [37]. Typically, green fluorescent protein (GFP) has a β‐barrel structure with 11 strands, in the middle of which is located a fluorescent chromophore [38]. The chromophore is protected by the barrel against interaction with external species, thus enabling a considerable emission efficiency.

Notably, β‐barrel may participate in the formation of small amyloid oligomers, which are often considered key neurotoxicants in Alzheimer's disease [39]. Another interesting structure associated with these diseases is the β‐helix, which is composed of parallel β‐strands and presents a helical protein structure [40]. β‐Helix is mainly stabilized by hydrogen‐bonding interaction, and sometimes electrostatic and hydrophobic effects also make a contribution. Remarkably, Schmuck et al. reported an octapeptide derivative with substituted N‐terminal group self‐assembles into a supramolecular β‐helix via head‐to‐tail intermolecular interactions, based on charge interactions between the individual peptides [41]. The peptide demonstrated intriguing transitions from small particles to helical fibers in a time‐variant process. And fibers may be switched to vesicles by modifying the pH value.

2.2.3 Turns

Turns are broadly defined as the regions of a peptide (and usually polypeptide) where a direction change in the backbone occurs [42]. They connect defined secondary structure regions in a protein and are thus necessary for protein compact. They generally take the forms of 16‐ (π‐turn) [43], 13‐ (α‐turn) [44], 10‐ (β‐turns) [45], and 7‐membered (γ‐turn) [46] H‐bonding rings (Figure 2.2c). Turns exhibit the characteristic dihedral angles depending on their types, and changing their sign usually converts them to their inverse form. Frequently occurring turn structures are γ‐turn and β‐turn, and β‐turn can participate in ring formation. These loops can induce orientation changes that occur within the β‐strand, which can lead to intramolecular folding and eventually an antiparallel β‐sheet structure.

2.3 Synthesis Strategies of Peptides

Many peptides have unique functions and commercial values. The investigation of peptide cannot leave peptide synthesis. Nowadays, there are majorly two ways to obtain a peptide: (i) direct chemical synthesis and (ii) biological engineering. Chemical synthesis of peptides underwent a long history since 1901, when Fischer and Fourneau created the term “peptide” [47]. After that, Bergmann and Zervas explored reversible Nα