Academic literature on the topic 'Self-assembling Amino Acid'

This study examined the formation of nanofiber hydrogels at neutral pH for 16 types of peptides with different net charges, hydrophobicities, and degrees of polymerization. The peptides formed various hydrogels depending on the arrangement of charged amino acids in the antiparallelβ-sheet structure. Circular dichroism (CD) measurement, atomic force microscopy (AFM), visible light spectroscopy, and dynamic viscoelasticity measurement showed that the formation of transparent nanofiber hydrogels in peptides requires at least 2 additional positively or negatively charged amino acids per peptide. When designing the amino acid sequence, it is important to consider both the net charge and position of the charged amino acids, and it should be ensured that basic amino acids do not face other basic ones in the antiparallelβ-sheet structure. Peptides that had charged amino acids clustered at the center of the nanofiber formed rigid gels.

Self-assembling peptides are a promising biomaterial with potential applications in medical devices and drug delivery. In the right combination of conditions, self-assembling peptides can form self-supporting hydrogels. Here, we describe how balancing attractive and repulsive intermolecular forces is critical for successful hydrogel formation. Electrostatic repulsion is tuned by altering the peptide’s net charge, and intermolecular attractions are controlled through the degree of hydrogen bonding between specific amino acid residues. We find that an overall net peptide charge of +/−2 is optimal to facilitate the assembly of self-supporting hydrogels. If the net peptide charge is too low then dense aggregates form, while a high molecular charge inhibits the formation of larger structures. At a constant charge, altering the terminal amino acids from glutamine to serine decreases the degree of hydrogen bonding within the assembling network. This tunes the viscoelastic properties of the gel, reducing the elastic modulus by two to three orders of magnitude. Finally, hydrogels could be formed from glutamine-rich, highly charged peptides by mixing the peptides in combinations with a resultant net charge of +/−2. These results illustrate how understanding and controlling self-assembly mechanisms through modulating intermolecular interactions can be exploited to derive a range of structures with tuneable properties.

The self-assembly and photophysical properties of 4-nitrophenylalanine (4NP) are changed with the alteration of solvent and final self-assembly state of 4NP in competitive solvent mixture and are dictated by the solvent ratio.

A pure l-amino acid-based molecular hydrogel was designed through conjugation of an anticancer tripeptide tyroservatide (YSV) with a self-assembling moiety, which enhanced therapeutic efficacy of both YSV and hydroxycamptothecin in vitro and in vivo.

Caries develops when the remineralization and demineralization equilibriums are out of balance. When the demineralization level exceeds 30%, the enamel suffers irreversible damage. As a result, non-invasive techniques for early detection and management of these reversible incipient lesions are recommended. Fluorides are the most important and effective, and their local efficacy has been widely researched. Many new innovations have been introduced for remineralisation of early lesion, such as ACP-CPP, Self-assembling peptides, etc., CPP–ACP is a milk product that aids in remineralization and dental caries prevention. Amorphous calcium phosphate is delivered by casein phosphopeptide, which also aids ACP binding to dental enamel. The natural amino acids Glutamine, Glutamic acid, Phenylalanine, Tryptophan, Serine, and Arginine make up the self-assembling peptide P11-4, which is intended to form brils at low pH and to be monomeric at higher pH. Furthermore, studies to be conducted to learn about the mechanism of Self assembling peptides.

Here we show that 4-aminocyclohexanecarboxylic acid is a rigid stretcher building block for the preparation of cyclic peptides that self-assemble to form peptide nanotubes with large diameter and hydrophobic pores.

Self-assembling peptides are currently attracting increasing interest as biological materials with a wide range of applications, including scaffolds for tissue engineering as well as drug delivery. The objective of the current work is to study the effect of amino acid size and charge distribution on the self-assembly and gelation behaviour of a series of de novo designed octapeptides.

L’objectif de ce travail de thèse est de développer de nouveaux agents tensioactifs, capables de s’auto-assembler sous forme de micelles permettant de solubiliser les principes actifs insolubles, en vue de leur administration par voie intraveineuse. Cette étude a permis la synthèse, la caractérisation physico-chimique ainsi que l’évaluation toxicologique in vitro et in vivo de nouveaux agents tensioactifs d’origine naturelle. Au cours de cette étude, différentes familles de tensioactifs ont été évaluées. Ces nouveaux agents tensioactifs sont composés d’une partie hydrophobe de type cholestérol, sels biliaires ou lipides, associée via une fonction amide à une partie hydrophile dérivée d’acides aminés tels que la lysine, la glutamine ou l’acide glutamique.Ces travaux expérimentaux ont permis d’étudier l’influence de la flexibilité de la partie hydrophobe sur la capacité de solubilisation des tensioactifs. Cette étude a montré que l’efficacité de solubilisation est reliée à la flexibilité de la partie hydrophobe. L’utilisation d’agents tensioactifs composés d’une chaîne lipidique saturée flexible a permis de solubiliser efficacement le principe actif insoluble avec un taux de charge de 46 % (m/m). Les tensioactifs composés de lipides saturés sont donc plus efficaces en termes de solubilisation que les dérivés de stéroïdes ou de lipides polyinsaturés, moins flexibles. Les études de toxicité ont mis en évidence la relation ente la structure chimique des tensioactifs et leur toxicité, en particulier vis-à-vis des membranes cellulaires. L’introduction de doubles liaisons en configuration cis dans la partie lipidique des tensioactifs permet de diminuer leur interaction avec les membranes cellulaires et donc leur toxicité mais diminue également leur capacité de solubilisation. Le développement de nouveaux agents tensioactifs nécessite donc de trouver un compromis entre la capacité de solubilisation et la toxicité des tensioactifs
The aim of this thesis was to develop novel surfactants, able to self-assemble into micelles and to solubilize insoluble drugs intented for intravenous injection. Natural-based surfactants were synthesized and their physico-chemical properties were evaluated. In addition, their in vitro and in vivo toxicity were evaluated. Their drug solubilization abitity was also investigated. Three surfactant classes were evaluated. They were composed of a hydrophobic moiety, such as cholesterol, bile salts or lipids, bonded to a hydrophilic moiety, deriving from amino acids, such as lysine, glutamine or glutamic acid, via an amide bond.The influence of surfactant hydrophobic moiety flexibility on drug solubilization ability was evaluated. This study evidenced that solubilization efficiency is related to the surfactant hydrophobic moiety flexibility. The use of surfactants with flexible and saturated lipidic moieties increased drug water solubility with a drug loading of 46 % (w/w). Saturated lipid-based surfactants exhibited a better solubilization efficiency, in comparison with steroid-based surfactants or poly-unsaturated-based surfactants. Toxicity studies evidenced the relation between surfactant chemical structure and their toxicity, in particular with cell membranes. The introduction of double bond in cis configuration in surfactant lipidic moiety decreased their interaction with cell membranes and thus their toxicity. In addition, this chemical modification also decreased their solubilization ability. To develop novel surfactants, it is thus necessary to take into account drug solubilization ability and toxicity of surfactants

This dissertation reports on the technology of cell-free protein synthesis (CFPS) including 1) stabilized lyophilized cell-free systems and 2) enhanced heterogeneous cell extracts. This work further considers applications of CFPS systems in 1) rapid vaccine development, 2) functional virus-based nanoparticles, 3) site-specific protein immobilization, and 4) expanding the language of biology using unnatural amino acids. CFPS technology is a versatile protein production platform that has many features unavailable in in vivo expression systems. The primary benefit cell-free systems provide is the direct access to the reaction environment, which is no longer hindered by the presence of a cell-wall. The “openness” of the system makes it a compelling candidate for many technologies. One limitation of CFPS is the necessity of freezing for long-term viable storage. We demonstrate that a lyophilized CFPS system is more stable against nonideal storage than traditional CFPS reagents. The Escherichia coli-based CFPS system in this work is limited by the biocatalytic machinery found natively in E. coli. To combat these limitations, exogenous biocatalysts can be expressed during fermentation of cells prepared into extract. We demonstrate that simple adjustments in the fermentation conditions can significantly increase the activity of the heterogeneous extract. Towards virus-based particles and vaccines, we demonstrate that the open nature of CFPS can be utilized for coexpression of virus proteins and self-assembly of virus particles. This technique allows for the rapid production of potential vaccines and novel functional virus-based nanoparticles. Unnatural amino acids expand the effective language of protein biology. Utilizing CFPS as an expression system, we demonstrated that the incorporation of a single specific unnatural amino acid allows for site-specific immobilization, thus stabilizing the protein against elevated temperatures and chemical denaturants. Current unnatural amino acid incorporation technologies are limited to one or few simultaneous incorporations and suffer from low efficiency. This work proposes a system that could potentially allow for upwards of 40 unnatural amino acids to be simultaneously incorporated, effectively tripling the protein code. These projects demonstrate the power and versatility of CFPS technologies while laying the foundation for promising technologies in the field of biotechnology.

"March 2003."
Thesis (Ph.D.)--Chinese University of Hong Kong, 2003.
Includes bibliographical references (p. 116-126).
Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Mode of access: World Wide Web.
Abstracts in English and Chinese.

本論文報道了 (a) 基於1,4-二取代 1,2,3-三唑的短肽類似物的合成及表徵，和 (b)這些類肽化合物在溶液相中的自組裝及凝膠化特性研究。
本論文第一章簡單地介紹及槪括基於三唑的寡聚物的構象和超分子的屬性。
本論文第二章報告1,4-二取代 1,2,3-三唑在類肽化合物中作為聯繫單元和作為構象控制的多功能性。
本論文第三章敍述了一類新的包含1,2,3-三唑在分子骨幹中的類肽化合物的合成及表徵。以炔丙胺/炔丁胺和 α-疊氮酸作為雙官能團前體，不同氨基酸成分和不同C-端基的系列類肽化合物由反覆的合成過程製備而來。用炔丙醇代替炔丙胺, 相應的酯類似物也被製備用作比較研究。
本論文第四章敍述了這些類肽化合物的自組裝及凝膠化特性。根據一維¹H 核磁共振，二維核磁共振 (2D)，氫/氘交換核磁共振 (H/D)， 蒸汽壓力均分子量 (VPO), 圓二色譜 (CD) 和紅外光譜分析研究，基於三唑類的短肽化合物Boc-aa¹aa²***aa[superscript n]-X 被發現以頭接尾的方式自我二聚 (K[subscript dsubscript isubscript m] ~10-680 M⁻¹)。二聚常數 (K[subscript dsubscript isubscript m])隨著氨基酸單位數目的增加而增大。在相同的寡聚系列中，K[subscript dsubscript isubscript m]值受到C-端基的大小的強烈影響。三肽類似物Boc-aa¹aa²aa³-X 還是許多芳烴類溶劑的優秀有機凝膠因子。掃描電子顯微技術(SEM)形態研究顯示三維網路形成於凝膠過程中。另一方面，結果顯示，類肽化合物的連結器長度在二級結構的形成和自組裝特性上發揮重要作用。
爲了進一步發展頭尾二聚的概念，本論文第五章敍述頭接尾的β-髮夾類似結構可通過適當的連結器偶聯兩個基於三唑的三肽類似物來獲得，如4-羥基脯氨酸的衍生物。一維¹H 核磁共振，二維核磁共振 (2D)，氫/氘交換核磁共振 (H/D)和紅外光譜等分析方法被用來研究其自組裝特性。
這篇論文展示了用三唑類體系結構設計類肽分子的可行性。產品結構表徵及性質探索的結果為這些新的類肽化合物的進一步調查和應用奠定了基礎。
This thesis reported (a) the synthesis and characterization of 1,4-disubstituted 1,2,3-triazole-based oligopeptides, and (b) the study on self assembling and gelation properties of the peptidomimetic compounds.
Chapter one gave a brief introduction and review on the click triazole-based oligomers, including their conformational and supramolecular properties.
Chapter two reviewed the versatility of 1,4-disubstituted 1,2,3-triazole unit as a linker and as a conformational controlling unit in peptidomimetics.
Chapter three disclosed the synthesis and characterization of a new class of linear peptidomimetics incorporating 1,2,3-triazoles in the backbone. Several series of click peptidomimetics, containing up to four amino acid residues and of different amino acid compositions and different C-terminal groups, were prepared by an iterative synthetic procedure, in which propargyl amine/homopropargyl amine and α-azido acids were used as bifunctional precursors. Using propargyl alcohol instead of propargyl amine, the corresponding ester analogs were also prepared for comparison studies.
In chapter four, the self-assembly and gelation properties of these peptidomimetics were illustrated. Click triazole-based oligopeptides Boc-aa¹aa²***aa[superscript n]-X (n = 2, 3 or 4) were found to self-dimerize (K[subscript dsubscript isubscript m] ~ 10-1020 M⁻¹) in a head-to-tail fashion according to ¹H NMR, two-dimensional NMR (2D), hydrogen/deuterium (H/D) exchange NMR, vapor pressure osmometry (VPO), circular dichroism (CD) and FT-IR studies. The dimerization constant (K[subscript dsubscript isubscript m]) was found to increase with increasing number of the amino acid units. Within the same oligomeric series, the K[subscript dsubscript isubscript m] value was strongly affected by the size of the C-terminal end group. The tripeptides Boc-aa¹aa²aa³-X were also excellent organogelators of many aromatic solvents. Morphological study indicated thata three-dimensional network was formed during the gelation process. On the other hand, the corresponding triester analog 98 and elongated analogs l-Boc-aa¹aa²aa³-Prg did not exhibit any self assembling properties. This revealed that the linker length and the amide units inside the click peptidomimetics played an important role in both the formation of secondary structures and the self-assembly properties.
To further develop the idea of head-to-tail dimerization, chapter five described the head-to-tail β-hairpin like structures could be obtained by conjugating two click triazole-based tripeptides through an appropriate linker such as derivatives of 4-hydroxyproline. Analytical methods, such as ¹H NMR, two-dimensional NMR, H/D exchange NMR spectroscopy, and FT-IR studies, were used to determine their self assembling properties.
This thesis has demonstrated the feasibility of designing peptidomimetic molecules with the triazole architecture. The results of the product characterization and property exploration have laid down the groundwork for further investigation and application of this new of peptidomimetic compounds.
Detailed summary in vernacular field only.
Detailed summary in vernacular field only.
Detailed summary in vernacular field only.
Detailed summary in vernacular field only.
Detailed summary in vernacular field only.
Detailed summary in vernacular field only.
Detailed summary in vernacular field only.
Ke, Zhihai.
Thesis (Ph.D.)--Chinese University of Hong Kong, 2012.
Includes bibliographical references (leaves 156-162).
Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Abstract also in Chinese.
Table of Contents --- p.i
Acknowledgements --- p.iv
Abbreviations --- p.v
Abstract --- p.vi
Publications related to this thesis --- p.x
Chapter Chapter One --- Click ChemistryA Powerful Tool to Create Supramolecular Chimeras
Chapter 1.1 --- Introduction to Click Chemistry --- p.1
Chapter 1.2 --- General Synthetic Strategies of Acyclic Oligotriazoles --- p.6
Chapter 1.3 --- Conformational Properties --- p.9
Chapter 1.3.1 --- Helical Structures from Oligotriazoles --- p.9
Chapter 1.3.2 --- Double Helical Structure from Oligotriazoles --- p.12
Chapter 1.3.3 --- β-Strands and β-sheets derived from Oligotriazoles --- p.13
Chapter 1.4 --- Supramolecular Properties --- p.14
Chapter 1.4.1 --- Host-guest Binding --- p.14
Chapter 1.4.2 --- Self Assembling Properties --- p.17
Chapter 1.4.3 --- Chemosensing Properties --- p.19
Chapter Chapter Two --- Click PeptidomimeticsTricks with Clicks
Chapter 2.1 --- Click ChemistryA New Ligation Tool for Peptidomimetics Synthesis --- p.20
Chapter 2.2 --- Click Peptidomimetics --- p.22
Chapter 2.2.1 --- Peptidepeptide --- p.23
Chapter 2.2.2 --- Polymerpeptide --- p.25
Chapter 2.2.3 --- Dendrimerpeptide --- p.26
Chapter 2.2.4 --- Small moleculepeptide --- p.27
Chapter 2.3 --- The triazole linkage as conformational control --- p.29
Chapter 2.3.1 --- Triazole-based β-turn mimetics --- p.29
Chapter 2.3.2 --- Cyclic turn mimetics --- p.31
Chapter 2.3.3 --- Cis/trans-prolyl mimic --- p.33
Chapter 2.3.4 --- Triazoles in helix bundles --- p.34
Chapter 2.4 --- Oligotriazole peptides --- p.35
Chapter 2.5 --- Summary and Aim of the Project --- p.36
Chapter Chapter Three --- Design, Synthesis and Characterization of Oligotriazole-based Peptidomimetics
Chapter 3.1 --- Synthetic Design --- p.38
Chapter 3.2 --- Choice of Reaction Conditions --- p.40
Chapter 3.3 --- Synthesis of Linear Click Triazole-based Peptidomimetics --- p.41
Chapter 3.3.1 --- Preparation of Click Triazole-based Peptidomimetics with Shorter Linkers --- p.42
Chapter 3.3.2 --- Preparation of Click Triazole-based Peptidomimetics l-Boc-aa¹aa²**aa[superscript n]-X with a Longer Spacer --- p.47
Chapter 3.3.3 --- Preparation of ester analogs and other model compounds --- p.49
Chapter 3.4 --- Characterization of Linear Click Triazole-based Peptidomimetics --- p.51
Chapter 3.4.1 --- Nuclear Magnetic Resonance (NMR) Spectroscopy --- p.52
Chapter 3.4.1.1 --- ¹H NMR Spectroscopy --- p.52
Chapter 3.4.1.2 --- ¹³C NMR Spectroscopy --- p.57
Chapter 3.4.2 --- Mass Spectrometry Analysis --- p.59
Chapter 3.4.3 --- High-performance Liquid Chromatography Analysis --- p.61
Chapter 3.5 --- Conclusions --- p.62
Chapter Chapter Four --- Self-Assembling Properties of Click Triazole-based Peptidomimetics
Chapter 4.1 --- Introduction --- p.63
Chapter 4.2 --- Results and Discussion --- p.65
Chapter 4.2.1 --- Nuclear Magnetic Resonance (NMR) Spectroscopy --- p.65
Chapter 4.2.1.1 --- Variable Concentration ¹H NMR --- p.65
Chapter 4.2.1.2 --- Two-dimensional ¹H NMR --- p.71
Chapter 4.2.1.3 --- Hydrogen/deuterium (H/D) exchange --- p.74
Chapter 4.2.2 --- Vapor Pressure Osmometry (VPO) --- p.77
Chapter 4.2.3 --- Infra-red (IR) Spectroscopy --- p.78
Chapter 4.2.4 --- Theoretical Calculation --- p.80
Chapter 4.2.5 --- Circular Dichroism (CD) --- p.81
Chapter 4.2.6 --- Gelation Behaviors --- p.83
Chapter 4.2.6.1 --- General Gelation Properties --- p.83
Chapter 4.2.6.2 --- Morphology Studies --- p.87
Chapter 4.3 --- Conclusions --- p.90
Chapter Chapter Five --- β-Hairpin Structure from Click Triazole-based Peptidomimetics
Chapter 5.1 --- Introduction and Design of β-hairpin --- p.91
Chapter 5.2 --- β-Hairpin Like Click Triazole-based Peptidomimetics Based on a Bifunctional Aromatic Linker 105 --- p.92
Chapter 5.3 --- β-Hairpin Like Click Peptidomimetics Based on a Proline Linker 113 --- p.97
Chapter 5.4 --- Conclusions --- p.107
Chapter Chapter Six --- Conclusion and Outlook --- p.109
Chapter Chapter Seven --- Experimental Procedures
Chapter 7.1 --- General Information --- p.112
Chapter 7.2 --- Experimental Procedures --- p.113
Chapter 7.3 --- Other Experimental --- p.152
References --- p.156
Chapter Appendix 1 --- (Nuclear Magnetic Resonance Spectra) --- p.A1
Appendix 2 --- p.A111

The ever-broadening scope of phage research has left behind the simplistic view of studying phages as just model systems in phage biology to a much broader application ranging from ecological management to immunity. Improved throughput technology in crystallography and structural studies has helped our understanding of these systems as supramolecular machines that possess the capacity of self-assembly. The idea of phages as self-assembling supramolecular nano-machines that are bioactive biomaterials in characteristics, tunable and easily producible have lent its utility to recent fields such as regenerative medicine and tissue engineering. Due to low metabolic activity and slow nutrient diffusion within cartilage, damage to this tissue often inevitably consist of slow and delayed regeneration and healing, the restriction of blood from reaching most part of this tissue and the resultant limitations in the availability of oxygen and other essential amino acids dictates a very slow systemic metabolic response also since transports system in this tissue have to employ less speedy forms. Cartilage regeneration therefore is a huge challenge. This chapter takes a look at the application of the phage display technology in cartilage tissue regeneration.