Methyl Group Research Articles

Insight into evolution characteristics of pyrolysis products of HLH and HL coal with Py-VUVPI-MS and DFT

To achieve a comprehensive understanding of the influence of chemical structure on the evolution characteristics of coal pyrolysis products, pyrolysis reaction of two kinds of low rank coal (Huolinhe and Huangling coal) were investigated with pyrolysis-vacuum ultraviolet photoionization mass spectrometry (Py-VUVPI-MS). The soft ionized mass spectral detection can provide evolved information of original pyrolysis product. The chemical structure of coal samples was characterized by solid-state 13C-NMR, indicating HLH coal with more branched chain and longer aliphatic chain structure. The bond dissociation enthalpies (BDE) of β-Cal-Cal and β-Cal-O within model compounds were obtained with density functional theory. The difference of peak temperature with maximum evolution was collected to investigate the effect of the chemical environment on evolution behavior of pyrolysis products. The results reveal that branched and long aliphatic side-chains can reduces BDE of β-Cal-Cal and β-Cal-O, resulting in the lower peak temperature of pyrolysis products derived from HLH coal. Substituent groups (such as alkyl and hydroxyl groups) attached on the aromatic rings can reduce peak temperatures. Moreover, the effects of the different substituted position on the aromatic ring of the methyl group presented on differences of the BDE. An increase in aromatic ring size correlates with a certain degree of reduction in BDE for β-Cal-Cal; consequently, peak temperature of pyrolysis products with larger aromatic rings is lower. The pyrolysis behavior of coal were discussed based on the experimental observations and theoretical calculation, which are beneficial to understand the reaction route and mechanism of coal pyrolysis.

Rheological and adhesive improvements of terminal blend rubberized asphalt via fumed silica nanoparticle modification

Due to the high degree of desulfurization and depolymerization of crumb rubber (CR) particles in terminal blend rubberized asphalt (TBRA), their elasticity and adhesive performance are insufficient. To address this, the study utilized low-cost fume silica nanoparticles (FSNPs) to enhance the elasticity and adhesive properties. TBRA binders with varying CR contents (30 %, 40 %, 50 %) were modified using different dosages of FSNPs (2 %, 4 %, 6 %). The microstructure of FSNPs was examined through TEM and SEM. Using a dynamic shear rheometer (DSR) test, contact angle test, and atomic force microscope (AFM) test, the effects of FSNPs on the rheological properties, surface energy, and adhesive properties of TBRA binders were evaluated. The results showed significant improvements in the deformation resistance and elasticity of the TBRA binders modified with FSNPs. This is attributed to the branched network structure of FSNPs, which notably enhances the binder's cohesion, thereby strengthening its resistance to shear deformation and improving elasticity. FSNPs effectively reduce the moisture sensitivity of TBRA, due to the hydrophilic hydroxyl groups on FSNPs being replaced by hydrophobic methyl groups (-CH3). The inadequate bonding performance of TBRA can be attributed to the high levels of extensively depolymerized and desulfurized CR particles, which reduce the cohesiveness of the binder. The addition of FSNPs, although it lowers the surface energy of TBRA binders, significantly enhances their cohesiveness due to the branched network structure, thereby improving their bond performance. AFM results indicate that FSNPs enhance the adhesive strength of the TBRA binder surface due to their high specific surface area, which provides more van der Waals forces and electrostatic interactions. For economic efficiency, an addition of 4 % is recommended for TB30, and 2 % for TB40 and TB50. At these specified concentrations, the bond strength of the TBRA binder can be increased by 45–55 %.

Cofactor binding triggers rapid conformational remodelling of the active site of a methyltransferase ribozyme

The methyltransferase ribozyme SMRZ-1 utilizes S-adenosyl-methionine (SAM) and Cu (II) ions to methylate RNA. Comparison of the SAM bound and unbound RNA structures has shown a conformational change in the RNA. However, the contribution of specific interactions and the role of a pseudo-triplex motif in the catalytic centre on the methylation reaction is not completely understood. In this study, we have used atomic substitutions and mutational analysis to investigate the reaction specificity and the key interactions required for catalysis. Substitution of the fluorescent nucleotide 2-aminopurine within the active ribozyme enabled the conformational dynamics of the RNA upon co-factor binding to be explored using fluorescence spectroscopy. We show that fast co-factor binding (t1/2 ∼ 0.7 seconds) drives a conformational change in the RNA to facilitate methyl group transfer. The importance of stacking interactions at the pseudo-triplex motif and chelation of the Cu (II) ion were shown to be essential for SAM binding.

200 Years of The Haloform Reaction: Methods and Applications.

Discovered in 1822, the haloform reaction is one of the oldest synthetic organic reactions. The haloform reaction enables the synthesis of carboxylic acids, esters or amides from methyl ketones. The reaction proceeds via exhaustive a-halogenation and then substitution by a nucleophile to liberate a haloform. The methyl group therefore behaves as a masked leaving group. The reaction methodology has undergone several important developments in the last 200 years, transitioning from a diagnostic test of methyl ketones to a synthetically useful tool for accessing complex esters and amides. The success of the general approach has been exhibited through the use of the reaction in the synthesis of many different complex molecules in fields ranging from natural product synthesis, pharmaceuticals, agrochemicals, fragrants and flavouring. The reaction has not been extensively reviewed since 1934. Therefore, herein we provide details of the history and mechanism of the haloform reaction, as well as an overview of the developments in the methodology and a survey of examples, particularly in natural product synthesis, in which the haloform reaction has been used.

Chitosan nanoparticles loaded with royal jelly: Characterization, antioxidant, antibacterial activities and in vitro digestion

Nano-embedding has appeared as a feasible technology to improve the high-quality utilization of royal jelly (RJ). Therefore, the ionic gelation method was proposed to prepared chitosan nanoparticles loaded with royal jelly (RJNPs) and the characterization and biological activity of RJNPs were evaluated in this study. Fourier-transform infrared spectroscopy, differential scanning calorimetry and X-ray diffraction results showed that the methyl and methylene groups of royal jelly combine with the amino groups of chitosan (CS) to become an amorphous polymer. In addition, the 48.68 % encapsulation efficiency and 31.90 % loading capacity were obtained under the optimal ratio of 1:1 RJ to CS, and the average particle size was <500 nm. The antioxidant activity of RJNPs gradually increased with the increase of the RJ proportion. Interestingly, the antibacterial activity on gram-positive bacteria was better than gram-negative bacteria. Most important, RJNPs exhibited better stability and digestibility rather than single RJ. Overall, these findings indicated that RJ can be embedded in chitosan, and RJNPs exhibited good thermal stability, antioxidant activity, antibacterial activities and bioavailability, which was important for the development and application of the high-quality utilization of RJ.

Vibronic Splitting of the Electronic Origin in Two Conformers of the 3-Tolunitrile Dimer.

3-tolunitrile (3-TN) can form three different dimers, which differ in the relative orientation of the methyl groups. We determined the geometry changes of two of these conformers of 3-TN upon electronic excitation via a Franck-Condon fit of the vibronic intensities in the fluorescence emission spectra. Both aromatic rings expand upon electronic excitation, showing a delocalized one-photon excitation of the cluster. The conformer with the smaller center-of-mass distance shows an unusual order of the split components of the electronic origin. We attribute this changed order to the stronger charge transfer contributions to the splitting and a partial breakdown of the point dipole approximation, made in the Frenkel type interaction.

Quantum-chemical study of alkyl- and alkenyladamantanes formation by ionic alkylation with olefins

In B3LYP-D3(BJ)/6-311++G** approximation thermodynamic parameters of formation reactions (total energy at 0 К, enthalpy and the Gibbs free energy at temperature 298.15 К and pressure 101325 Pa) are assessed for the products of ionic alkylation of adamantane and lower alkyladamantanes with ethylene and propylene. Aluminium chloride was used as acid catalyst model. Quantum-chemical calculations demonstrate the influence of methyl groups in adamantanes and olefin molecular weight on energetics of formation of relevant alkyl- and alkenyladamantanes.

Catalytic undirected methylation of unactivated C(sp3)-H bonds suitable for complex molecules.

In pharmaceutical discovery, the "magic methyl" effect describes a substantial improvement in the pharmacological properties of a drug candidate with the incorporation of methyl groups. Therefore, to expedite the synthesis of methylated drug analogs, late-stage, undirected methylations of C(sp3)-H bonds in complex molecules would be valuable. However, current methods for site-selective methylations are limited to activated C(sp3)-H bonds. Here we describe a site-selective, undirected methylation of unactivated C(sp3)-H bonds, enabled by photochemically activated peroxides and a nickel(II) complex whose turnover is enhanced by an ancillary ligand. The methodology displays compatibility with a wide range of functional groups and a high selectivity for tertiary C-H bonds, making it suitable for the late-stage methylation of complex organic compounds that contain multiple alkyl C-H bonds, such as terpene natural products, peptides, and active pharmaceutical ingredients. Overall, this method provides a synthetic tool to explore the "magic methyl" effect in drug discovery.

DNA-binding proteins from MBD through ZF to BEN: recognition of cytosine methylation status by one arginine with two conformations.

Maintenance methylation, of palindromic CpG dinucleotides at DNA replication forks, is crucial for the faithful mitotic inheritance of genomic 5-methylcytosine (5mC) methylation patterns. MBD proteins use two arginine residues to recognize symmetrically-positioned methyl groups in fully-methylated 5mCpG/5mCpG and 5mCpA/TpG dinucleotides. In contrast, C2H2 zinc finger (ZF) proteins recognize CpG and CpA, whether methylated or not, within longer specific sequences in a site- and strand-specific manner. Unmethylated CpG sites, often within CpG island (CGI) promoters, need protection by protein factors to maintain their hypomethylated status. Members of the BEN domain proteins bind CGCG or CACG elements within CGIs to regulate gene expression. Despite their overall structural diversity, MBD, ZFand BEN proteins all use arginine residues to recognize guanine, adopting either a 'straight-on' or 'oblique' conformation. The straight-on conformation accommodates a methyl group in the (5mC/T)pG dinucleotide, while the oblique conformation can clash with the methyl group of 5mC, leading to preferential binding of unmethylated sequences.

Research on modeling the lignin waste molecular structure and pyrolytic reactions using ReaxFF MD method

The lack of clarity in characterizing the chemical structure model of lignin waste hinders the comprehensive understanding of its pyrolysis reaction mechanism. The characterization results revealed that the de–alkalized lignin sample contained larger amounts of aliphatic and aromatic carbons compared to carbonyl carbons. Additionally, the aliphatic carbon molecules exhibited a higher presence of oxygenated carbons. The degree of aromaticity (fa) was determined to be 63.93 %. The resulting single–molecule structural model exhibited a molecular formula of C33H26O11 and a molecular weight of 598.56. Furthermore, the evolutions patterns and formation pathways of primary volatile components (H2, CH4, CO, and CO2) in pyrolysis reactions were revealed. The number of H2 molecules exhibited a positive correlation with the rise in pyrolysis reaction temperature. CH4 molecules exhibited a pattern of initially increasing and subsequently decreasing. The number of CO molecules exhibited a positive correlation with the rise in pyrolysis temperature. Conversely, the number of CO2 molecules demonstrated an initial increase followed by a decrease as the pyrolysis temperature increased. Finally, the generation pathway analysis of pyrolysis products shows that the H2 molecule is composed of two hydrogen atoms bonded together that have been dissociated from the carboxyl group. Alternatively, it can be produced through hydrogenation reactions involving hydrogen atoms detached from the carboxyl group and methyl groups. CH4 is primarily generated through the reaction between –CH3 and free hydrogen ions. CO is primarily produced through the cleavage of the carbonyl group. CO2 is primarily produced through the cleavage of carboxyl and ester groups.

MecE, MecB, and MecC proteins orchestrate methyl group transfer during dichloromethane fermentation.

Dichloromethane (DCM), a common hazardous industrial chemical, is anaerobically metabolized by four bacterial genera: Dehalobacter, Dehalobacterium, Ca. Dichloromethanomonas, and Ca. Formimonas. However, the pivotal methyltransferases responsible for DCM transformation have remained elusive. In this study, we investigated the DCM catabolism of Dehalobacterium formicoaceticum strain EZ94, contained in an enriched culture, using a combination of biochemical approaches. Initially, enzymatic assays were conducted with cell-free protein extracts, after protein separation by blue native polyacrylamide gel electrophoresis. In the slices with the highest DCM transformation activity, a high absolute abundance of the methyltransferase MecC was revealed by mass spectrometry. Enzymatic activity assays with heterologously expressed MecB, MecC, and MecE from strain EZ94 showed complete DCM transformation only when all three enzymes were present. Our experimental results, coupled with the computational analysis of MecB, MecC, and MecE sequences, enabled us to assign specific roles in DCM transformation to each of the proteins. Our findings reveal that both MecE and MecC are zinc-dependent methyltransferases responsible for DCM demethylation and re-methylation of a product, respectively. MecB functions as a cobalamin-dependent shuttle protein transferring the methyl group between MecE and MecC. This study provides the first biochemical evidence of the enzymes involved in the anaerobic metabolism of DCM.IMPORTANCEDichloromethane (DCM) is a priority regulated pollutant frequently detected in groundwater. In this work, we identify the proteins responsible for the transformation of DCM fermentation in Dehalobacterium formicoaceticum strain EZ94 using a combination of biochemical approaches, heterologous expression of proteins, and computational analysis. These findings provide the basis to apply these proteins as biological markers to monitor bioremediation processes in the field.

Clinician's Guide to Epitranscriptomics: An Example of N1-Methyladenosine (m1A) RNA Modification and Cancer.

Epitranscriptomics is the study of modifications of RNA molecules by small molecular residues, such as the methyl (-CH3) group. These modifications are inheritable and reversible. A specific group of enzymes called "writers" introduces the change to the RNA; "erasers" delete it, while "readers" stimulate a downstream effect. Epitranscriptomic changes are present in every type of organism from single-celled ones to plants and animals and are a key to normal development as well as pathologic processes. Oncology is a fast-paced field, where a better understanding of tumor biology and (epi)genetics is necessary to provide new therapeutic targets and better clinical outcomes. Recently, changes to the epitranscriptome have been shown to be drivers of tumorigenesis, biomarkers, and means of predicting outcomes, as well as potential therapeutic targets. In this review, we aimed to give a concise overview of epitranscriptomics in the context of neoplastic disease with a focus on N1-methyladenosine (m1A) modification, in layman's terms, to bring closer this omics to clinicians and their future clinical practice.

Henkel‐like Decarboxylation Produces Mononuclear Arylalkalis, [4‐(CH3)3N(C6H4)M]+ which Hydrolyse and Undergo Surprising SN2 Reactions Between Alkali Hydroxides and (CH3)3NC6H5+

AbstractBenzoate substituted with a cationic quaternary ammonium group at the para‐position, [4‐(CH3)3N(C6H4)CO2], forms mononuclear alkali metal ion complexes, [4‐(CH3)3N(C6H4)CO2M]+ (M=Li, Na, K, Rb and Cs), which are observed by electrospray‐ionisation mass spectrometry. When mass selected and subjected to collision‐induced dissociation each of these complexes undergoes decarboxylation to produce the mononuclear arylalkali complex cations, [4‐(CH3)3N(C6H4)M]+, which subsequently react with water via hydrolysis to yield the quaternary ammonium cation, (CH3)3NC6H5+. The unexpected product ions, [M((CH3)2NC6H5)]+, [M(CH3OH)]+, and M+, which are associated with the hydrolysis pathway, suggest an unusual reaction occurring within the exit channel ion‐molecule complex, [(CH3)3NC6H5+MOH]+. DFT calculations were used to examine the: decarboxylation reaction of [4‐(CH3)3N(C6H4)CO2M]+, which readily proceeds via a four‐centred transition state; the hydrolysis and SN2 reactions accounting for formation of products in the exit channel, which are connected via a roaming mechanism in which the metal hydroxide moiety migrates from the para‐hydrogen of (CH3)3NC6H5+ to one of the methyl groups.

Thermotropic “Plumber's Nightmare”—A Tight Liquid Organic Double Framework

AbstractGyroid, double diamond and the body‐centred “Plumber's nightmare” are the three most common bicontinuous cubic phases in lyotropic liquid crystals and block copolymers. While the first two are also present in solvent‐free thermotropics, the latter had never been found. Containing six‐fold junctions, it was unlikely to form in the more common phases with rod‐like cores normal to the network columns, where a maximum of four branches can join at a junction. The solution has therefore been sought in side‐branched mesogens that lie in axial bundles joined at their ends by flexible “hinges”. But for the tightly packed double framework, geometric models predicted that the side‐chains should be very short. The true Plumber's nightmare reported here, using fluorescent dithienofluorenone rod‐like mesogen, has been achieved with, indeed, no side chains at all, but with 6 flexible end‐chains. Such molecules normally form columnar phases, but the key to converting a complex helical column–forming mesogen into a framework‐forming one was the addition of just one methyl group to each pendant chain. A geometry‐based explanation is given.

Catalytic oxidation of butylated hydroxytoluene using thermally treated cobalt-copper layered double hydroxides: Synthesis, structural evolution, and mechanistic insights

This study investigates the application of cobalt-copper layered double hydroxides (LDHs) in the oxidation of butylated hydroxytoluene (BHT) and explores their catalytic behavior during thermal treatment. LDHs were synthesized via coprecipitation, and various ratios of Co-Cu hydrotalcite were subjected to thermal treatment. Structural analysis revealed that thermal treatment transforms the LDHs into mixed metal oxides. Among the synthesized catalysts, Co1Cu3-LDHs exhibited superior catalytic activity in the oxidation of BHT. Techniques such as XRD, FT-IR, TGA, N2 adsorption-desorption, SEM, and XPS were employed to investigate the structural changes and surface properties of the LDHs. The Co1Cu3-LDH catalyst, treated at 250 °C, exhibited outstanding catalytic performance, attributed to the synergistic effects between Co and Cu. Upon optimizing the reaction conditions, the conversion of BHT reached 99 %, with a selectivity of 77 % towards 3,5-di‑tert‑butyl‑4-hydroxybenzaldehyde (BHT-CHO). The oxidation mechanism involves the oxidation of the π-electron system on the benzene ring and deep oxidation of the phenolic hydroxyl methyl group, with two potential reaction pathways proposed.

Ligand-Controlled Regiodivergent Ring Expansion of Benzosilacyclobutenes with Alkynes en Route to Axially Chiral Silacyclohexenyl Arenes.

A ligand-controlled regiodivergent and enantioselective ring expansion of benzosilacyclobutenes with internal naphthyl alkynes has been achieved by adjusting the ligand cavity size. The ligand (S)-8H-binaphthyl phosphoramidite, featuring small methyl groups on its arms, provides a spacious cavity that favors sterically demanding Si-Csp3 ring expansion, predominantly yielding axially chiral (S)-1-silacyclohexenyl arenes. In contrast, the ligand (R)-spiro phosphoramidite, with bulky t-Bu groups on its arms, offers a compact cavity that facilitates less sterically demanding Si-Csp2 ring expansion, leading primarily to axially chiral (S)-2-silacyclohexenyl arenes. Density functional theory calculations delineate distinct mechanistic pathways for each ring expansion route and elucidate their regio- and enantioselectivity.

Multisite-assisted design of asymmetric silicon-bridged diphosphine ligands for selective ethylene tri-/tetramerization

A series of novel silicon-bridged asymmetric diphosphine ligands (PNSiP-type L1-L3 and PCSiP-type L4) and their corresponding Cr(Ⅲ) catalysts have been synthesized and evaluated for ethylene tri-/tetramerization. When DMAO/AlEt3 was used as a co-catalyst, catalyst 1 based on ligand L1, with a cyclopentyl group on the N atom and two methyl groups on the Si atom, showed the highest catalytic activity of 8.21 kg g-1 Cr/h with 90.45 % combined (60.53 % 1-C6= + 29.92 % 1-C8=) selectivity. Moreover, the catalytic system based on catalyst 1 achieved a remarkable selectivity for 1-C8= of 62.58 % at 15 °C, even though polymers were the main products. Catalyst 2 based on ligand L2, bearing a cyclopentyl group at N and one methyl and one phenyl group on the Si moiety, exhibited a catalytic activity of 8.09 kg g-1 Cr/h accompanied with 71.61 % 1-C6= and 14.12 % 1-C8=product selectivity. Catalyst 3 based on ligand L3 having an isopropyl group on the N atom and two methyl groups on the Si atom, displayed 6.95 kg g-1 Cr/h catalytic activity with 69.06 % 1-C6= and 17.88 % 1-C8=product selectivity. Catalyst 4 based on PCSiP-type ligand L4, showed poor catalytic activity and 79.15 % of high 1-C6= selectivity. Compared with the previously reported long-chain Cr(Ⅲ) catalysts based on silicon-bridged diphosphine ligands (PNSiCP-/PCSiCP-type), Cr(Ⅲ) catalysts based on short-chain PNSiP-type and PCSiP-type ligands designed in this work exhibited higher ethylene oligomerization performance. Among them, PNSiP-type ligands are more inclined to generate 1-C8= than PCSiP-type ligand, and reducing the steric bulk of substituents on the Si atom in PNSiP-type ligands is also beneficial for 1-C8= generation. Density functional theory (DFT) calculations also revealed that the PNSiP-type catalysts could exhibit excellent ethylene trimerization performance. The DFT calculations thus provide a theoretical foundation for a deeper understanding of the ethylene tri-/tetramerization mechanism and designing of new ligand structures.

Synthesis and crystal structure of poly[ethanol(μ-4-methyl-pyridine N-oxide)di-μ-thio-cyanato-cobalt(II)

Reaction of 4-methyl-pyridine N-oxide and Co(NCS)2 in ethanol as solvent accidentally leads to the formation of single crystals of Co(NCS)2(4-methyl-pyridine N-oxide)(ethanol) or [Co(NCS)2(C6H7NO)(C2H6O)] n . The asymmetric unit of the title compound consists of one CoII cation, two crystallographically independent thio-cyanate anions, one 4-methyl-pyridine N-oxide coligand and one ethanol mol-ecule on general positions. The cobalt cations are sixfold coordinated by one terminal and two bridging thio-cyanate anions, two bridging 4-methyl-pyridine N-oxide coligands and one ethanol mol-ecule, with a slightly distorted octa-hedral geometry. The cobalt cations are linked by single μ-1,3(N,S)-bridging thio-cyanate anions into corrugated chains, that are further connected into layers by pairs of μ-1,1(O,O)-bridging 4-methyl-pyridine N-oxide coligands. The layers are parallel to the bc plane and are separated by the methyl groups of the 4-methyl-pyridine N-oxide coligands. Within the layers, intra-layer hydrogen bonding is observed.

The Membrane Dipole Potential and the Roles of Interfacial Water and Lipid Hydrocarbon Chains.

Understanding membrane charge transport processes, including the actions of ion channels, pumps, carriers, and membrane-active peptides, requires a description of the electrostatics of the lipid bilayer. We have simulated a library of different lipid chemistries to reveal the impact of the headgroup, glycerol backbone, and hydrocarbon chains on the membrane dipole potential. We found a strong dependence of the potential on lipid packing, but this was not caused by the packing of lipid polar components, due to cancellation of their electric fields by electrolyte. In contrast, lipid tail contributions were determined by area per lipid, arising from two countering effects. Increased area per lipid leads to chain tilting that increases methylene dipole projections to strengthen the electric field within the bilayer, while at the same time decreasing the electric field from terminal methyl groups. Moreover, electric fields from some nonterminal groups and the terminal methyl group can extend beyond the bilayer center and be canceled by the opposing leaflet. This interleaflet field annulment explains the experimental reduction in dipole potential for unsaturated and branched lipid bilayers, by as much as ∼200 mV, as well as experiments that substitute chain carbons with sulfur. Replacing ester with ether groups (eliminating two carbonyl groups) causes a significant reduction in potential, also by ∼200 mV, in agreement with experiment. We show that the effect can be largely attributed to the loss of aligned water molecules in the glycerol backbone region, lowering the potential inside the bilayer core. When only one of the two carbonyls is removed (using a hybrid ester-ether lipid or a single-chain lipid), most of this reduction in potential was lost, with the single carbonyl group able to maintain full hydration in the interfacial region. While headgroup chemistry can have a major effect (by as much as ±100 mV relative to phosphatidylcholine), anionic headgroups either decrease or increase the dipole potential, with the variation involving perturbation in hydrogen-bonded water molecules and changes in packing of lipid tails. Overall, these results suggest that membrane electrostatics are dominated by aligned water molecules at the polar-hydrocarbon interface and, surprisingly, by the charge distribution of the nonpolar lipid tails, and not the packing of headgroup and glycerol carbonyl dipoles.

Structure Derivatization of IgG-Binding Peptides and Analysis of Their Secondary Structure by Circular Dichroism Spectroscopy.

Mid-sized cyclic peptides are a promising modality for modern drug discovery. Their larger interaction area coupled with an appropriate secondary structure is more suitable than small molecules for binding to the target protein. In this study, we conducted a structure derivatization of an immunoglobulin G (IgG)-binding peptide (15-IgBP), a β-hairpin-like cyclic peptide with a twisted β-strand and assessed the effect of the secondary structure on IgG-binding activity using circular dichroism (CD) spectra analysis. As a result, derivatization at the Ala5 and Gly9 positions affected the secondary structure of 15-IgBP, in particular the appearance of a small positive peak in the 220-240 nm region characteristic of 15-IgBP in the CD spectrum. Maintaining this peak at a moderate level may be important for the expression of IgG binding activity. We found the small methyl group at Ala5 to be crucial for retaining the preferred secondary structure; we also found Gly9 could be replaced by D-amino acids. By integrating these findings with previous results of the structure-activity relationship, we obtained four potent affinity peptides for IgG binding (Kd = 4.24-5.85 nM). Furthermore, we found the Gly9 position can be substituted for D-Lys. This is a new potential site for attaching functional units for conjugation with IgG for the preparation of homogeneous antibody-drug conjugates.