Core Motif Research Articles

Various Flesh: George Herbert Wells’s The Invisible Man

『투명 인간』에서의 핵심 모티브는 과학이라는 도구를 이용하여 인간 육체의 변형을 시도하는 것이다.『투명 인간』의 주인공 그리핀은 과학을 힘을 이용해 당연히 ‘보이고, 보여야 하는’ 인간의 육체를 ‘보이지 않게’ 변형하려고 한다. 인간의 힘으로 육체를 변형하려는 시도는 신의 영역의 힘을 보유하려는 것이며, 대타자의 시선의 장에서 주체를 숨기려는 것이다. 대타자의 시선에서의 사라짐으로서 그리핀은 거세된 주체의 욕망을 부인하고 더 나아가 숨어서 비밀스럽게 초월적인 힘을 드러내려고 한다. 한편으로 그리핀의 욕망은 투명 인간이 된 이후 추적을 피해 달아나는 과정에서 발현되는 사회변혁에 대한 갈망이다. 직접적으로 텍스트에서 언급되는 공포정치는 그가 나아가려는 목표로의 노정일 수도 있다.『투명 인간』이 보여주는 과학은 시선과 육체의 어떤 관계를, 인간의 한정된 능력치의 눈이 볼 수 있는 범위를, 우리가 본다고 믿는 것과 실제로 보지 못하는 것을 환기 시킨다. 투명 인간은 사회를 변혁시키려다 극명하게 소외된 주체의 전형을 보여 준다. 그가 얻는 것은 자유 또는 욕망의 실현 대신 존재의 소멸뿐이다. 부랑자가 숨긴 그리핀의 비밀 노트는 이후의 사회변혁의 가능성을 잠재태로 남기는 은유일지도 모른다.The core motif in The Invisible Man is an attempt to transform the human body by using the tools of science. Griffin, the protagonist of The Invisible Man is employing the power of science when he tries to transform the human body that can be and should be seen into ‘invisible’ body. Leaving the Other’s gaze, Griffin denies the desire of the castrated subject, and further seeks to reveal transcendent power secretly. Reign of Terror, which is mentioned directly in the text, may be the course of his goal. The science in the text evokes the relationship of the body and gaze, the limited ability of the human eyes, we believe, what we can see but actually don’t look at. The Invisible Man indicates the specimens of subjects that are clearly alienated after the very trial for transforming society. He is forced to disappear without freedom or desire. Griffin’s secret notes hidden by the bum might be a metaphor of a potential for the future social reformation.

Genome wide analysis of W-box element in Arabidopsis thaliana reveals TGAC motif with genes down regulated by heat and salinity

To design, synthetic promoters leading to stress-specific induction of a transgene, the study of cis-regulatory elements is of great importance. Cis-regulatory elements play a major role in regulating the gene expression spatially and temporally at the transcriptional level. The present work focuses on one of the important cis-regulatory element, W-box having TGAC as a core motif which serves as a binding site for the members of the WRKY transcription factor family. In the present study, we have analyzed the occurrence frequency of TGAC core motifs for varying spacer lengths (ranging from 0 to 30 base pairs) across the Arabidopsis thaliana genome in order to determine the biological and functional significance of these conserved sequences. Further, the available microarray data was used to determine the role of TGAC motif in abiotic stresses namely salinity, osmolarity and heat. It was observed that TGAC motifs with spacer sequences like TGACCCATTTTGAC and TGACCCATGAATTTTGAC had a significant deviation in frequency and were thought to be favored for transcriptional bindings. The microarray data analysis revealed the involvement of TGAC motif mainly with genes down-regulated under abiotic stress conditions. These results were further confirmed by the transient expression studies with promoter-reporter cassettes carrying TGAC and TGAC-ACGT variant motifs with spacer lengths of 5 and 10.

Plant Defensin Peptides have Antifungal and Antibacterial Activity Against Human and Plant Pathogens.

Plant defensins are small, cysteine-rich antimicrobial peptides. These peptides have previously been shown to primarily inhibit the growth of fungal plant pathogens. Plant defensins have a γ-core motif, defined as GXCX3-9C, which is required for their antifungal activity. To evaluate plant defensins as a potential control for a problematic agricultural disease (alfalfa crown rot), short, chemically synthesized peptides containing γ-core motif sequences were screened for activity against numerous crown rot pathogens. These peptides showed both antifungal and, surprisingly, antibacterial activity. Core motif peptides from Medicago truncatula defensins (MtDef4 and MtDef5) displayed high activity against both plant and human bacterial pathogens in vitro. Full-length defensins had higher antimicrobial activity compared with the peptides containing their predictive γ-core motifs. These results show the future promise for controlling a wide array of economically important fungal and bacterial plant pathogens through the transgenic expression of a plant defensin. They also suggest that plant defensins may be an untapped reservoir for development of therapeutic compounds for combating human and animal pathogens.

Indolylvinyl Ketones: Building Blocks for the Synthesis of Natural Products and Bioactive Compounds

Indolylvinyl ketones are valuable building blocks that can be utilized for the synthesis of numerous natural products and bioactive molecules containing an indole core motif. Herein, we describe their application for the total synthesis of some alkaloids, their analogues, and a variety of other important compounds, with an emphasis on biologically active examples.1 Introduction2 Functionalization of the Enone C=C Bond2.1 Reduction2.2 Michael Addition2.3 Cycloaddition3 Transformation of the Carbonyl Group3.1 Reduction3.2 Knoevenagel Reaction3.3 Addition of Organometallic Compounds3.4 Olefination4 Reactions Involving the Enone Conjugate System С=С–С=О4.1 Reactions with 1,2-Dinucleophiles4.2 Reactions with Compounds Bearing an Active Methylene Group4.3 Reactions with 1,3-Dinucleophiles4.4 Reactions with 1,4-Dinucleophiles5 Functionalization of the Enone Methylene Group C(O)–CH2R5.1 Acylation/Crotonic Condensation and Related Transformations5.2 Enolization6 Functionalization of the Indole Core6.1 [4+2] Cycloaddition6.2 [3+3] Annulation6.3 Electrocyclic Reactions7 Miscellaneous8 Conclusions

Pecos River Style Rock Art: A Prehistoric Iconography by James Burr Harrison Macrae

Reviewed by: Pecos River Style Rock Art: A Prehistoric Iconography by James Burr Harrison Macrae Timothy K. Perttula Pecos River Style Rock Art: A Prehistoric Iconography. By James Burr Harrison Macrae. (College Station: Texas A&M University Press, 2018. Pp. 112. Illustrations, bibliography, index.) James Burr Harrison Macrae’s Pecos River Style Rock Art primarily concerns the structure and character of Pecos River Style painted rock art, which dates from ca. 4,000–1,500 years ago and is found in rock shelters in the lower Pecos River area in the West Texas and Mexican Chihuahuan Desert. This rock art was produced by painters in Middle and Late Archaic-period-hunter-fisher-gatherer societies who seasonally ranged across the land. The book also represents the author’s efforts to explain and understand both the rock art and the aboriginal peoples who created it. The polychrome painted rock art, in red, black, yellow, and white pigment-based paint, features elongated linear and abstract anthromorphs as well as a wide variety of other core and non-core motifs. Macrae makes a strong case that the rock art has both “metaphorical and spiritual connection to the landscape” (73), and was meant to convey ritual and supernatural events, religious precepts as well as cosmology, and depict the hierarchy of important men and leaders in their society. Chapter 1 introduces the reader to the Lower Pecos region, its geology (especially its limestone overhangs, which were used as rock art panels) and climate, and the archaeological context of the rock art. Most interestingly, it also includes autobiographical information about the author and his decision to focus academically on the Pecos River Style art. In chapter 2, Macrae provides the methods and theoretical approach he employs in the study of the rock art. Here, Macrae characterizes the approach as structural-iconographic analysis. This analysis relies on the identification of repetitive patterns and symbols in the art, along with determining the contextual relationships between the symbols and patterns in each rock art panel at rock shelter sites. Macrae follows this by defining nineteen core motifs in the rock art imagery in chapter 3. The imagery is divided into anthropomorphs, material culture, and zoomorphs (mainly mountain lions, deer, and birds, as well as centipedes), enigmatic characters, and geometric symbols combined into an abstract and symbolic narrative on “paintings layered one on top of another” (30). The heart of the book arrives in chapter 4 with the presentation of [End Page 459] Macrae’s well-illustrated typology of those nineteen core motifs along with fifty-five non-core motifs and symbols identified in the Pecos River Style rock art. This typology includes a description of the unique character of these motifs as well as interpretations of their symbolic meaning offered by Macrae and a variety of rock art researchers. These interpretations represent the best current view of their meaning, “subject to the best available evidence and theory” (36). Macrae ties together these disparate pieces of information and symbolic content on Pecos River style rock art in Chapter 5. He argues that this rock art was created by hunter-fisher-gatherer groups as part of a long-term ritual cycle tied to periods of social pressure and stress among Lower Pecos bands. During periods of increasing populations or aridity, the rock art functioned “as a stabilizing and unifying cultural process” that was manifest as cyclical nucleation of bands and the creation of sacred space “at natural shrines on the landscape” (77). I highly recommend Macrae’s book to readers interested in the aboriginal rock art of the Lower Pecos region, as well as in the author’s research approach. I hope Macrae will continue his studies of Pecos River Style rock art and delve further into the complex rock art created by Lower Pecos peoples. Timothy K. Perttula Austin, Texas Copyright © 2019 The Texas State Historical Association

Improved smallest peptides based on positive charge increase of the γ-core motif from PνD1 and their mechanism of action against Candida species.

BackgroundPlant defensins have a hallmark γ-core motif (GXCX3-9C) that is related to their antimicrobial properties. The aim of this work was to design synthetic peptides based on the region corresponding to the PvD1 defensin γ-core that are the smallest amino acid sequences that bear the strongest biological activity.MethodsWe made rational substitutions of negatively charged amino acid residues with positively charged ones, and the reduction in length in the selected PvD1 γ-core sequence to verify whether the increased net positive charges and shortened length are related to the increase in antifungal activity. Herein, we opted to evaluate the action mechanism of γ33-41PvD1++ peptide due to its significant inhibitory effect on tested yeasts. In addition, it is the smallest construct comprising only nine amino acid residues, giving it a better possibility to be a prototype for designing a new antifungal drug, with lower costs to the pharmaceutical industry while still maintaining the strongest antimicrobial properties.ResultsThe γ33-41PvD1++ peptide caused the most toxic effects in the yeast Candida buinensis, leading to membrane permeabilization, viability loss, endogenous reactive oxygen species increase, the activation of metacaspase, and the loss of mitochondrial functionality, suggesting that this peptide triggers cell death via apoptosis.ConclusionWe observed that the antifungal activity of PvD1 is not strictly localized in the structural domain, which comprises the γ-core region and that the increase in the net positive charge is directly related to the increase in antifungal activity.

Hexanuclear Cu3O-3Cu triazole-based units as novel core motifs for high nuclearity copper(ii) frameworks.

The asymmetric 3,5-disubstituted 1,2,4-triazole ligand H2V (5-amino-3-picolinamido-1,2,4-triazole) by reaction with an excess of Cu(ii) perchlorate (Cu : H2V being 12 : 1) has produced a novel hexanuclear {Cu6(μ3-O/H)(HV/V)3} fragment, with one triangular Cu3(μ3-O/H) group connected to three peripheral single Cu(ii) ions through a cis–cis–trans bridging mode of the ligand, which is the building block of the three structures described here: one hexanuclear, [Cu6(μ3-O)(HV)3(ClO4)7(H2O)9]·8H2O (1), one dodecanuclear, [Cu12(μ3-O)2(V)6(ClO4)5(H2O)18](ClO4)3·6H2O (2), and one tetradecanuclear 1D-polymer, {[Cu14(μ3-OH)2(V)6(HV)(ClO4)11(H2O)20](ClO4)2·14H2O}n (3), the last two containing hexanuclear subunits linked by perchlorato bridges. The Cu–Cu av. intra-triangle distance is 3.352(2) Å and the Cu(central)–Cu(bridged external) av. distance is 5.338(3) Å. The magnetic properties of the hexanuclear “Cu3O–3Cu” cluster have been studied, resulting as best fit parameters: g = 2.18(1), J(intra-triangle) = −247.0(1) cm−1 and j(central CuII – external CuII) = −5.15(2) cm−1.

The effects of maternal diet on adaptive changes in the brain melanocortin 4 receptors in female offspring

Anaplasmosis is one of the most prevalent tick-borne diseases of cattle caused by Anaplasma marginale. MSP1a surface protein has been shown to be involved in eliciting immunity to infected cattle. Carbon nanotubes (CNTs) has been increasingly highlighted due to their needle like structure, which contain multiple attachment sites for biomolecules and may interact with or cross biological membranes, increasing antigen availability to immune system. Here, we have successfully designed a nanocomplex of a synthetic peptide noncovalently attached to multiwalled CNT (MWCNT). Peptide comprising the core motif of the MSP1a was efficiently adsorb onto the nanoparticle surface. The MWCNT-Am1 nanocomplex exhibited high stability and good dispersibility and in vivo immunization showed high levels of IgG1 and IgG2a, followed by increased expression of pro-inflammatory and anti-inflammatory cytokines. This is a proof-of-concept of a nanovaccine that was able to generate a strong immune response compared to the common antigen-adjuvant vaccine without the nanoparticles.

Arabidopsis ADF5 promotes stomatal closure by regulating actin cytoskeleton remodeling in response to ABA and drought stress.

Stomatal movement plays an essential role in plant responses to drought stress, and the actin cytoskeleton and abscisic acid (ABA) are two important components of this process. Little is known about the mechanism underlying actin cytoskeleton remodeling and the dynamic changes occurring during stomatal movement in response to drought stress/ABA signaling. Actin-depolymerizing factors (ADFs) are conserved actin severing/depolymerizing proteins in eukaryotes, and in angiosperms ADFs have evolved actin-bundling activity. Here, we reveal that the transcriptional expression of neofunctionalized Arabidopsis ADF5 was induced by drought stress and ABA treatment. Furthermore, we demonstrated that ADF5 loss-of-function mutations increased water loss from detached leaves, reduced plant survival rates after drought stress, and delayed stomatal closure by regulating actin cytoskeleton remodeling via its F-actin-bundling activity. Biochemical assays revealed that an ABF/AREB transcription factor, DPBF3, could bind to the ADF5 promoter and activate its transcription via the ABA-responsive element core motif ACGT/C. Taken together, our findings indicate that ADF5 participates in drought stress by regulating stomatal closure, and may also serve as a potential downstream target of the drought stress/ABA signaling pathway via members of the ABF/AREB transcription factors family.

Discovery and optimization of pyrazole amides as antagonists of CCR1

A HTS screen for CCR1 antagonists afforded a novel sub-micromolar hit 5 containing a pyrazole core. In this report the design, optimization, and SAR of novel CCR1 antagonists based on a pyrazole core motif is presented. Optimization led to the advanced candidate compounds (S)-16q and (S)-16r with 250-fold improved CCR1 potency, excellent off-target selectivity and attractive drug-like properties.

Flexibility and structure of flanking DNA impact transcription factor affinity for its core motif.

Spatial and temporal expression of genes is essential for maintaining phenotype integrity. Transcription factors (TFs) modulate expression patterns by binding to specific DNA sequences in the genome. Along with the core binding motif, the flanking sequence context can play a role in DNA–TF recognition. Here, we employ high-throughput in vitro and in silico analyses to understand the influence of sequences flanking the cognate sites in binding of three most prevalent eukaryotic TF families (zinc finger, homeodomain and bZIP). In vitro binding preferences of each TF toward the entire DNA sequence space were correlated with a wide range of DNA structural parameters, including DNA flexibility. Results demonstrate that conformational plasticity of flanking regions modulates binding affinity of certain TF families. DNA duplex stability and minor groove width also play an important role in DNA–TF recognition but differ in how exactly they influence the binding in each specific case. Our analyses further reveal that the structural features of preferred flanking sequences are not universal, as similar DNA-binding folds can employ distinct DNA recognition modes.

Analogues of Muraymycin Nucleoside Antibiotics with Epimeric Uridine-Derived Core Structures.

Nucleoside analogues have found widespread application as antiviral and antitumor agents, but not yet as antibacterials. Naturally occurring uridine-derived ‘nucleoside antibiotics’ target the bacterial membrane protein MraY, an enzyme involved in peptidoglycan biosynthesis and a promising target for the development of novel antibacterial agents. Muraymycins represent a nucleoside-peptide subgroup of such MraY-inhibiting natural products. As part of detailed structure-activity relationship (SAR) studies on muraymycins and their analogues, we now report novel insights into the effects of stereochemical variations in the nucleoside core structure. Using a simplified version of the muraymycin scaffold, it was shown that some formal inversions of stereochemistry led to about one order of magnitude loss in inhibitory potency towards the target enzyme MraY. In contrast, epimers of the core motif with retained inhibitory activity were also identified. These 5′,6′-anti-configured analogues might serve as novel chemically tractable variations of the muraymycin scaffold for the future development of uridine-derived drug candidates.

Lanthanide(III)-Catalyzed Synthesis of trans-Diaminocyclopentenones from Substituted Furfurals and Secondary Amines via a Domino Ring-Opening/4π-Electrocyclization Pathway.

A strategy toward the synthesis of trans-4,5-diaminocyclopent-2-enones is described. This core motif is embedded in the marine sponge derived alkaloids agelamadin B and nagelamide J. A variety of 2-substituted trans-4,5-diaminocyclopent-2-enones were synthesized in good to quantitative yields using lanthanide(III) catalysis. The products were formed exclusively as the trans-diastereomers via a mechanism in which the C4-C5 bond formation occurs through a 4π-conrotatory electrocyclization. The precursor 3-substituted furfurals can be readily accessed using palladium(0)-catalyzed cross-coupling between 3-bromofurfural and boronic acids, trifluoroborate salts, or alkynes.

Active Natural Product Scaffolds against Trypanosomatid Parasites: A Review

Neglected tropical diseases caused by trypanosomatid parasites are a continuing and escalating problem, which devastate the less economically developed cultures in countries in which they are endemic by impairing both human and animal health. Current drugs for these diseases are regarded as out-of-date and expensive, with unacceptable side-effects and mounting parasite resistance, meaning there is an urgent need for new therapeutics. Natural products have long been a source of potent, structurally diverse bioactive molecules. Herein are reviewed natural products with reported trypanocidal activity, which have been clustered based on core structural similarities, to aid the future discovery of new trypanocidal core motifs with potential routes to synthetically accessible natural product cores suggested.

Discovering epistatic feature interactions from neural network models of regulatory DNA sequences.

MotivationTranscription factors bind regulatory DNA sequences in a combinatorial manner to modulate gene expression. Deep neural networks (DNNs) can learn the cis-regulatory grammars encoded in regulatory DNA sequences associated with transcription factor binding and chromatin accessibility. Several feature attribution methods have been developed for estimating the predictive importance of individual features (nucleotides or motifs) in any input DNA sequence to its associated output prediction from a DNN model. However, these methods do not reveal higher-order feature interactions encoded by the models.ResultsWe present a new method called Deep Feature Interaction Maps (DFIM) to efficiently estimate interactions between all pairs of features in any input DNA sequence. DFIM accurately identifies ground truth motif interactions embedded in simulated regulatory DNA sequences. DFIM identifies synergistic interactions between GATA1 and TAL1 motifs from in vivo TF binding models. DFIM reveals epistatic interactions involving nucleotides flanking the core motif of the Cbf1 TF in yeast from in vitro TF binding models. We also apply DFIM to regulatory sequence models of in vivo chromatin accessibility to reveal interactions between regulatory genetic variants and proximal motifs of target TFs as validated by TF binding quantitative trait loci. Our approach makes significant strides in improving the interpretability of deep learning models for genomics.Availability and implementationCode is available at: https://github.com/kundajelab/dfim.Supplementary information Supplementary data are available at Bioinformatics online.

PixelDB: Protein–peptide complexes annotated with structural conservation of the peptide binding mode

PixelDB, the Peptide Exosite Location Database, compiles 1966 non-redundant, high-resolution structures of protein-peptide complexes filtered to minimize the impact of crystal packing on peptide conformation. The database is organized to facilitate study of structurally conserved versus non-conserved elements of protein-peptide engagement. PixelDB clusters complexes based on the structural similarity of the peptide-binding protein, and by comparing complexes within a cluster highlights examples of domains that engage peptides using more than one binding mode. PixelDB also identifies conserved peptide core structural motifs characteristic of each binding mode. Peptide regions that flank core motifs often make non-structurally conserved interactions with the protein surface in regions we call exosites. Many examples establish that exosite contacts can be important for enhancing protein binding and interaction specificity. PixelDB provides a resource for computational and structural biologists to study, model, and predict core-motif and exosite-contacting peptide interactions. PixelDB is available to the community without restriction in a convenient flat-file format with accompanying visualization tools.

Shared nucleotide flanks confer transcriptional competency to bZip core motifs.

Sequence-specific DNA binding recruits transcription factors (TFs) to the genome to regulate gene expression. Here, we perform high resolution mapping of CEBP proteins to determine how sequence dictates genomic occupancy. We demonstrate a fundamental difference between the sequence repertoire utilized by CEBPs in vivo versus the palindromic sequence preference reported by classical in vitro models, by identifying a palindromic motif at <1% of the genomic binding sites. On the native genome, CEBPs bind a diversity of related 10 bp sequences resulting from the fusion of degenerate and canonical half-sites. Altered DNA specificity of CEBPs in cells occurs through heterodimerization with other bZip TFs, and approximately 40% of CEBP-binding sites in primary human cells harbor motifs characteristic of CEBP heterodimers. In addition, we uncover an important role for sequence bias at core-motif-flanking bases for CEBPs and demonstrate that flanking bases regulate motif function across mammalian bZip TFs. Favorable flanking bases confer efficient TF occupancy and transcriptional activity, and DNA shape may explain how the flanks alter TF binding. Importantly, motif optimization within the 10-mer is strongly correlated with cell-type-independent recruitment of CEBPβ, providing key insight into how sequence sub-optimization affects genomic occupancy of widely expressed CEBPs across cell types.

The Role of the Arginine in the Conserved N-Terminal Domain RLFDQxFG Motif of Human Small Heat Shock Proteins HspB1, HspB4, HspB5, HspB6, and HspB8.

Although the N-terminal domain of vertebrate small heat shock proteins (sHsp) is poorly conserved, it contains a core motif preserved in many members of the sHsp family. The role of this RLFDQxFG motif remains elusive. We analyzed the specific role of the first arginine residue of this conserved octet sequence in five human sHsps (HspB1, HspB4, HspB5, HspB6, and HspB8). Substitution of this arginine with an alanine induced changes in thermal stability and/or intrinsic fluorescence of the related HspB1 and HspB8, but yielded only modest changes in the same biophysical properties of HspB4, HspB5, and HspB6 which together belong to another clade of vertebrate sHsps. Removal of the positively charged Arg side chain resulted in destabilization of the large oligomers of HspB1 and formation of smaller size oligomers of HspB5. The mutation induced only minor changes in the structure of HspB4 and HspB6. In contrast, the mutation in HspB8 was accompanied by shifting the equilibrium from dimers towards the formation of larger oligomers. We conclude that the RLFDQxFG motif plays distinct roles in the structure of several sHsp orthologs. This role correlates with the evolutionary relationship of the respective sHsps, but ultimately, it reflects the sequence context of this motif.

Exploring the functionalisation of the thieno[2,3-d]pyrimidinedione core: Late stage access to highly substituted 5-carboxamide-6-aryl scaffolds

The thieno[2,3-d]pyrimidinedione core is found as a component in a range of pharmaceutically active compounds, however, synthetic approaches to these scaffolds rely on access to functionalised, highly substituted thiophenes. Here we describe a new approach for the preparation of 5-carboxamide-6-aryl analogues that involves a two-step synthesis of the thieno[2,3-d]pyrimidinedione core from a readily available mercaptouracil derivative. Thio-alkylation with ethyl 3-bromopyruvate, followed by cyclisation and dehydration mediated by polyphosphoric acid allowed the scalable synthesis of the thieno[2,3-d]pyrimidinedione unit. The late-stage functionalisation of this core motif via bromination of the thiophene ring and a subsequent Suzuki-Miyaura reaction as the key steps permitted access to a novel library of 5-carboxamide-6-aryl analogues. The physicochemical properties of these compounds were determined, generating an insight into the potential bioavailability of these scaffolds. Based on these results, a selection of the novel 5-carboxamide-6-aryl analogues were tested as lactate uptake inhibitors of monocarboxylate transporters 1, 2 and 4 in Xenopus oocytes.

Tuning the Condensation Degree of {FeIIIn} Oxo Clusters via Ligand Metathesis, Temperature, and Solvents.

Trinuclear μ3-oxo-centered iron(III) isobutyrate clusters readily react with polyalcohol organic ligands under one-pot synthesis conditions. Depending on the ligand, solvent, and temperature, a range of hexa-, dodeca-, and doicosanuclear iron(III) oxo-hydroxo condensation products, isolated as (mdeaH3)2[Fe6O(thme)4Cl6]·0.5(MeCN)·0.5(H2O) (1), [Fe12O4(OH)2(teda)4(N3)4(MeO)4]N3(NO3)0.5(MeO)0.5·2.5(H2O) (2), [Fe12O6(teda)4Cl8]·6(CHCl3) (3), [Fe22O16(OH)2(O2CCHMe2)18(bdea)6(EtO)2(H2O)2]·2(EtOH)·5(MeCN)·6(H2O) (4), and [Fe22O14(OH)4(O2CCHMe2)18(mdea)6(EtO)2(H2O)2](NO3)2·EtOH·H2O (5), where tedaH4 = N, N, N', N'-tetrakis(2-hydroxyethyl)ethylenediamine; thmeH3 = 1,1,1-tris(hydroxymethyl)ethane; mdeaH2 = N-methyldiethanolamine; and bdeaH2 = N-butyldiethanolamine. Complete carboxylate metathesis in the {Fe3} precursor complexes by thme3- or teda4- and the agglomeration of the formed species under solvothermal conditions afforded carboxylate-free {Fe6} product (1) in MeCN/CH2Cl2 or {Fe12} complexes (2 and 3) in MeOH/EtOH and CHCl3/thf, respectively (thf = tetrahydrofuran). Single-crystal X-ray diffraction analyses revealed that 1 contains a [Fe6O(thme)4Cl6]2- cluster anion with a Lindqvist-type {Fe6(μ6-O)} core motif, charge-compensated by two protonated mdeaH3+ cations. 2 comprises a [Fe12O4(OH)2(teda)4(N3)4(MeO)4]2+ cation with a {Fe12O4(OH)2}26+ core, whereas 3 contains a charge-neutral [Fe12O6(teda)4(Cl)8] complex with an {Fe12O6}24+ core. Finally, employing flexible bdeaH2 or mdeaH2 ligands under soft reaction conditions afforded giant {Fe22} oxo-hydroxo complexes (4 and 5) with a central {Fe6} layer sandwiched between two outer {Fe8} groups. Magnetic studies of 1-5 revealed strong antiferromagnetic coupling between the FeIII spin centers in all clusters.